{"id":520,"date":"2016-08-19T15:59:42","date_gmt":"2016-08-19T15:59:42","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/?post_type=chapter&#038;p=520"},"modified":"2016-08-19T15:59:43","modified_gmt":"2016-08-19T15:59:43","slug":"chapter-16-gene-expression","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/chapter\/chapter-16-gene-expression\/","title":{"raw":"Chapter\u00a016.\u00a0Gene Expression","rendered":"Chapter\u00a016.\u00a0Gene Expression"},"content":{"raw":"<div class=\"chapter\" title=\"Chapter&#xA0;16.&#xA0;Gene Expression\" id=\"id516614\"><div class=\"titlepage\"><div><div><h1 class=\"title\"><span class=\"cnx-gentext-chapter cnx-gentext-autogenerated\">Chapter\u00a0<\/span><span class=\"cnx-gentext-chapter cnx-gentext-n\">16<\/span><span class=\"cnx-gentext-chapter cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-chapter cnx-gentext-t\">Gene Expression<\/span><\/h1><\/div><\/div><\/div><div class=\"introduction\" id=\"m44533\"><div id=\"m44533-fig-ch16_00_01\" class=\"figure splash\" title=\"Figure&#xA0;16.1.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44533-fs-id1435492\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155830\/Figure_16_00_01.jpg\" width=\"700\" alt=\"Part A depicts a cross section of an eyeball, which has a lens at the front and a cluster of blood vessels at the back. Part B depicts a liver, which is shaped like a triangle. Beneath the liver is a lobe-shaped gall bladder connected to a pancreas by a stem-like vessel. Part C is a sketch, drawn by Leonardo Da Vinci, of a man standing erect with outstretched arms. Superimposed on this image, the man has his legs spread and his arms uplifted.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">The genetic content of each somatic cell in an organism is the same, but not all genes are expressed in every cell. The control of which genes are expressed dictates whether a cell is (a) an eye cell or (b) a liver cell. It is the differential gene expression patterns that arise in different cells that give rise to (c) a complete organism.<\/div><\/div><h3 class=\"title\"><span>Introduction<sup><a href=\"co03.html#book-attribution-m44533\">*<\/a><\/sup><\/span><\/h3><p><span id=\"m44533-fs-id1595873\"> <\/span>Each somatic cell in the body generally contains the same DNA. A few exceptions include red blood cells, which contain no DNA in their mature state, and some immune system cells that rearrange their DNA while producing antibodies. In general, however, the genes that determine whether you have green eyes, brown hair, and how fast you metabolize food are the same in the cells in your eyes and your liver, even though these organs function quite differently. If each cell has the same DNA, how is it that cells or organs are different? Why do cells in the eye differ so dramatically from cells in the liver?<\/p><p><span id=\"m44533-fs-id2059567\"> <\/span>Whereas each cell shares the same genome and DNA sequence, each cell does not turn on, or express, the same set of genes. Each cell type needs a different set of proteins to perform its function. Therefore, only a small subset of proteins is expressed in a cell. For the proteins to be expressed, the DNA must be transcribed into RNA and the RNA must be translated into protein. In a given cell type, not all genes encoded in the DNA are transcribed into RNA or translated into protein because specific cells in our body have specific functions. Specialized proteins that make up the eye (iris, lens, and cornea) are only expressed in the eye, whereas the specialized proteins in the heart (pacemaker cells, heart muscle, and valves) are only expressed in the heart. At any given time, only a subset of all of the genes encoded by our DNA are expressed and translated into proteins. The expression of specific genes is a highly regulated process with many levels and stages of control. This complexity ensures the proper expression in the proper cell at the proper time.<\/p><\/div><div xml:lang=\"en\" class=\"section module\" title=\"16.1.&#xA0;Regulation of Gene Expression\"><div class=\"titlepage\"><div><div><h2 id=\"m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<sup><a href=\"co03.html#book-attribution-m44534\">*<\/a><\/sup><\/span><\/span><\/h2><\/div><div class=\"abstract\"><div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"\/><\/span><\/span><\/div><p>By the end of this section, you will be able to:\n<\/p><div class=\"itemizedlist\"><ul class=\"itemizedlist\"><li class=\"listitem\"><p>Discuss why every cell does not express all of its genes<\/p><\/li><li class=\"listitem\"><p>Describe how prokaryotic gene regulation occurs at the transcriptional level<\/p><\/li><li class=\"listitem\"><p>Discuss how eukaryotic gene regulation occurs at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels<\/p><\/li><\/ul><\/div><\/div><\/div><\/div><div class=\"toc\"><ul><li class=\"toc-section\"><a href=\"#m44534-fs-id2300410\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic versus Eukaryotic Gene Expression<\/span><\/a><\/li><\/ul><\/div><p><span id=\"m44534-fs-id1367090\"> <\/span>For a cell to function properly, necessary proteins must be synthesized at the proper time. All cells control or regulate the synthesis of proteins from information encoded in their DNA. The process of turning on a gene to produce RNA and protein is called <em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1684185\"> <\/span>gene expression<\/em><a id=\"id517191\" class=\"indexterm\">. Whether in a simple unicellular organism or a complex multi-cellular organism, each cell controls when and how its genes are expressed. For this to occur, there must be a mechanism to control when a gene is expressed to make RNA and protein, how much of the protein is made, and when it is time to stop making that protein because it is no longer needed.<\/a><\/p><p><span id=\"m44534-fs-id2989558\"> <\/span>The regulation of gene expression conserves energy and space. It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required. In addition, only expressing a subset of genes in each cell saves space because DNA must be unwound from its tightly coiled structure to transcribe and translate the DNA. Cells would have to be enormous if every protein were expressed in every cell all the time.<\/p><p><span id=\"m44534-fs-id2626522\"> <\/span>The control of gene expression is extremely complex. Malfunctions in this process are detrimental to the cell and can lead to the development of many diseases, including cancer.<\/p><div class=\"section\" title=\"Prokaryotic versus Eukaryotic Gene Expression\"><div class=\"titlepage\"><div><div><h3 id=\"m44534-fs-id2300410\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic versus Eukaryotic Gene Expression<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44534-fs-id2011802\"> <\/span>To understand how gene expression is regulated, we must first understand how a gene codes for a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different manners.<\/p><p><span id=\"m44534-fs-id2988639\"> <\/span>Prokaryotic organisms are single-celled organisms that lack a cell nucleus, and their DNA therefore floats freely in the cell cytoplasm. To synthesize a protein, the processes of transcription and translation occur almost simultaneously. When the resulting protein is no longer needed, transcription stops. As a result, the primary method to control what type of protein and how much of each protein is expressed in a prokaryotic cell is the regulation of DNA transcription. All of the subsequent steps occur automatically. When more protein is required, more transcription occurs. Therefore, in prokaryotic cells, the control of gene expression is mostly at the transcriptional level.<\/p><p><span id=\"m44534-fs-id1446467\"> <\/span>Eukaryotic cells, in contrast, have intracellular organelles that add to their complexity. In eukaryotic cells, the DNA is contained inside the cell\u2019s nucleus and there it is transcribed into RNA. The newly synthesized RNA is then transported out of the nucleus into the cytoplasm, where ribosomes translate the RNA into protein. The processes of transcription and translation are physically separated by the nuclear membrane; transcription occurs only within the nucleus, and translation occurs only outside the nucleus in the cytoplasm. The regulation of gene expression can occur at all stages of the process (<a class=\"xref target-figure\" href=\"ch16.html#m44534-fig-ch16_01_01\" title=\"Figure&#xA0;16.2.&#xA0;\">Figure\u00a016.2<\/a>). Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (<em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1688359\"> <\/span>epigenetic<\/em><a id=\"id517288\" class=\"indexterm\"> level), when the RNA is transcribed (transcriptional level), when the RNA is processed and exported to the cytoplasm after it is transcribed (<em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1688363\"> <\/span>post-transcriptional<\/em><\/a><a id=\"id517303\" class=\"indexterm\"> level), when the RNA is translated into protein (translational level), or after the protein has been made (<em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1688368\"> <\/span>post-translational<\/em><\/a><a id=\"id517317\" class=\"indexterm\"> level).<\/a><\/p><div id=\"m44534-fig-ch16_01_01\" class=\"figure\" title=\"Figure&#xA0;16.2.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44534-fs-id1568395\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155833\/Figure_16_01_01.jpg\" width=\"550\" alt=\"Prokaryotic cells do not have a nucleus, and DNA is located in the cytoplasm. Ribosomes attach to the mRNA as it is being transcribed from DNA. Thus, transcription and translation occur simultaneously. In eukaryotic cells, the DNA is located in the nucleus, and ribosomes are located in the cytoplasm. After being transcribed, pre-mRNA is processed in the nucleus to make the mature mRNA, which is then exported to the cytoplasm where ribosomes become associated with it and translation begins.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">Prokaryotic transcription and translation occur simultaneously in the cytoplasm, and regulation occurs at the transcriptional level. Eukaryotic gene expression is regulated during transcription and RNA processing, which take place in the nucleus, and during protein translation, which takes place in the cytoplasm. Further regulation may occur through post-translational modifications of proteins.<\/div><\/div><p><span id=\"m44534-fs-id1444103\"> <\/span>The differences in the regulation of gene expression between prokaryotes and eukaryotes are summarized in <a class=\"xref target-table\" href=\"ch16.html#m44534-tab-ch16_01_01\" title=\"Table&#xA0;16.1.&#xA0;\">Table\u00a016.1<\/a>. The regulation of gene expression is discussed in detail in subsequent modules.<\/p><div class=\"table\" id=\"m44534-tab-ch16_01_01\"><table cellpadding=\"0\" style=\"border: 1px solid; border-spacing: 0px;\"><caption><span class=\"cnx-gentext-caption cnx-gentext-t\">Table <\/span><span class=\"cnx-gentext-caption cnx-gentext-n\">16.1. <\/span><\/caption><thead valign=\"bottom\"><tr><th colspan=\"2\" style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">Differences in the Regulation of Gene Expression of Prokaryotic and Eukaryotic Organisms<\/th><\/tr><tr><th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Prokaryotic organisms<\/th><th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">Eukaryotic organisms<\/th><\/tr><\/thead><tbody valign=\"top\"><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: left !important;\">Lack nucleus<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">Contain nucleus<\/td><\/tr><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: left !important;\">DNA is found in the cytoplasm<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">DNA is confined to the nuclear compartment<\/td><\/tr><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: left !important;\">RNA transcription and protein formation occur almost simultaneously<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">RNA transcription occurs prior to protein formation, and it takes place in the nucleus. Translation of RNA to protein occurs in the cytoplasm.<\/td><\/tr><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: left !important;\">Gene expression is regulated primarily at the transcriptional level<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 0 !important; text-align: left !important;\">Gene expression is regulated at many levels (epigenetic, transcriptional, nuclear shuttling, post-transcriptional, translational, and post-translational)<\/td><\/tr><\/tbody><\/table><\/div><div id=\"m44534-fs-id2853732\" class=\"note evolution\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Evolution Connection<\/span><\/div><div class=\"body\"><p title=\"Evolution of Gene Regulation\"><span id=\"m44534-fs-id2054814\"> <\/span><\/p><div class=\"title\"><b>Evolution of Gene Regulation<\/b><\/div><p title=\"Evolution of Gene Regulation\">Prokaryotic cells can only regulate gene expression by controlling the amount of transcription. As eukaryotic cells evolved, the complexity of the control of gene expression increased. For example, with the evolution of eukaryotic cells came compartmentalization of important cellular components and cellular processes. A nuclear region that contains the DNA was formed. Transcription and translation were physically separated into two different cellular compartments. It therefore became possible to control gene expression by regulating transcription in the nucleus, and also by controlling the RNA levels and protein translation present outside the nucleus.<\/p><p><span id=\"m44534-fs-id1435492\"> <\/span>Some cellular processes arose from the need of the organism to defend itself. Cellular processes such as gene silencing developed to protect the cell from viral or parasitic infections. If the cell could quickly shut off gene expression for a short period of time, it would be able to survive an infection when other organisms could not. Therefore, the organism evolved a new process that helped it survive, and it was able to pass this new development to offspring.<\/p><\/div><\/div><\/div><\/div><div xml:lang=\"en\" class=\"section module\" title=\"16.2.&#xA0;Prokaryotic Gene Regulation\"><div class=\"titlepage\"><div><div><h2 id=\"m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<sup><a href=\"co03.html#book-attribution-m44535\">*<\/a><\/sup><\/span><\/span><\/h2><\/div><div class=\"abstract\"><div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"\/><\/span><\/span><\/div><p>By the end of this section, you will be able to:\n<\/p><div class=\"itemizedlist\"><ul class=\"itemizedlist\"><li class=\"listitem\"><p>Describe the steps involved in prokaryotic gene regulation<\/p><\/li><li class=\"listitem\"><p>Explain the roles of activators, inducers, and repressors in gene regulation<\/p><\/li><\/ul><\/div><\/div><\/div><\/div><div class=\"toc\"><ul><li class=\"toc-section\"><a href=\"#m44535-fs-idm82649424\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>trp<\/em><\/span> Operon: A Repressor Operon<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44535-fs-idm202194608\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Catabolite Activator Protein (CAP): An Activator Regulator<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44535-fs-idm146228272\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>lac<\/em><\/span> Operon: An Inducer Operon<\/span><\/a><\/li><\/ul><\/div><p><span id=\"m44535-fs-idm200418880\"> <\/span>The DNA of prokaryotes is organized into a circular chromosome supercoiled in the nucleoid region of the cell cytoplasm. Proteins that are needed for a specific function, or that are involved in the same biochemical pathway, are encoded together in blocks called <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1254793\"> <\/span>operons<\/em><a id=\"id517973\" class=\"indexterm\">. For example, all of the genes needed to use lactose as an energy source are coded next to each other in the lactose (or <span class=\"emphasis\"><em>lac<\/em><\/span>) operon.<\/a><\/p><p><span id=\"m44535-fs-idm204458112\"> <\/span>In prokaryotic cells, there are three types of regulatory molecules that can affect the expression of operons: repressors, activators, and inducers. <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1254811\"> <\/span>Repressors<\/em><a id=\"id518002\" class=\"indexterm\"> are proteins that suppress transcription of a gene in response to an external stimulus, whereas <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1254815\"> <\/span>activators<\/em><\/a><a id=\"id518016\" class=\"indexterm\"> are proteins that increase the transcription of a gene in response to an external stimulus. Finally, inducers are small molecules that either activate or repress transcription depending on the needs of the cell and the availability of substrate.<\/a><\/p><div class=\"section\" title=\"The trp Operon: A Repressor Operon\"><div class=\"titlepage\"><div><div><h3 id=\"m44535-fs-idm82649424\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>trp<\/em><\/span> Operon: A Repressor Operon<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44535-fs-idm166815232\"> <\/span>Bacteria such as <span class=\"emphasis\"><em>E. coli<\/em><\/span> need amino acids to survive. <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1676419\"> <\/span>Tryptophan<\/em><a id=\"id518058\" class=\"indexterm\"> is one such amino acid that <span class=\"emphasis\"><em>E. coli<\/em><\/span> can ingest from the environment. <span class=\"emphasis\"><em>E. coli<\/em><\/span> can also synthesize tryptophan using enzymes that are encoded by five genes. These five genes are next to each other in what is called the <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1676435\"> <\/span>tryptophan (<span class=\"emphasis\"><em>trp<\/em><\/span>) operon<\/em><\/a><a id=\"id518091\" class=\"indexterm\"> (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_01\" title=\"Figure&#xA0;16.3.&#xA0;\">Figure\u00a016.3<\/a>). If tryptophan is present in the environment, then <span class=\"emphasis\"><em>E. coli<\/em><\/span> does not need to synthesize it and the switch controlling the activation of the genes in the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is switched off. However, when tryptophan availability is low, the switch controlling the operon is turned on, transcription is initiated, the genes are expressed, and tryptophan is synthesized.<\/p><div id=\"m44535-fig-ch16_02_01\" class=\"figure\" title=\"Figure&#xA0;16.3.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44535-fs-idm229109280\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155835\/Figure_16_02_01.jpg\" width=\"450\" alt=\"The trp operon has a promoter, an operator, and five genes named trpE, trpD, trpC, trpB, and trpA that are located in sequential order on the DNA. RNA polymerase binds to the promoter. When tryptophan is present, the trp repressor binds the operator and prevents the RNA polymerase from moving past the operator; therefore, RNA synthesis is blocked. In the absence of tryptophan, the repressor dissociates from the operator. RNA polymerase can now slide past the operator, and transcription begins.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">The five genes that are needed to synthesize tryptophan in <span class=\"emphasis\"><em>E. coli<\/em><\/span> are located next to each other in the <span class=\"emphasis\"><em>trp<\/em><\/span> operon. When tryptophan is plentiful, two tryptophan molecules bind the repressor protein at the operator sequence. This physically blocks the RNA polymerase from transcribing the tryptophan genes. When tryptophan is absent, the repressor protein does not bind to the operator and the genes are transcribed.<\/div><\/div><p><span id=\"m44535-fs-idm174533984\"> <\/span>A DNA sequence that codes for proteins is referred to as the coding region. The five coding regions for the tryptophan biosynthesis enzymes are arranged sequentially on the chromosome in the operon. Just before the coding region is the <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1391232\"> <\/span>transcriptional start site<\/em><a id=\"id518195\" class=\"indexterm\">. This is the region of DNA to which RNA polymerase binds to initiate transcription. The promoter sequence is upstream of the transcriptional start site; each operon has a sequence within or near the promoter to which proteins (activators or repressors) can bind and regulate transcription.<\/a><\/p><p><span id=\"m44535-fs-idm199850336\"> <\/span>A DNA sequence called the operator sequence is encoded between the promoter region and the first <span class=\"emphasis\"><em>trp<\/em><\/span> coding gene. This <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1391250\"> <\/span>operator<\/em><a id=\"id518225\" class=\"indexterm\"> contains the DNA code to which the repressor protein can bind. When tryptophan is present in the cell, two tryptophan molecules bind to the <span class=\"emphasis\"><em>trp<\/em><\/span> repressor, which changes shape to bind to the <span class=\"emphasis\"><em>trp<\/em><\/span> operator. Binding of the tryptophan\u2013repressor complex at the operator physically prevents the RNA polymerase from binding, and transcribing the downstream genes.<\/a><\/p><p><span id=\"m44535-fs-idm101642592\"> <\/span>When tryptophan is not present in the cell, the repressor by itself does not bind to the operator; therefore, the operon is active and tryptophan is synthesized. Because the repressor protein actively binds to the operator to keep the genes turned off, the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is negatively regulated and the proteins that bind to the operator to silence <span class=\"emphasis\"><em>trp<\/em><\/span> expression are <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1619494\"> <\/span>negative regulators<\/em><a id=\"id518276\" class=\"indexterm\">.<\/a><\/p><div id=\"m44535-fs-idm187290400\" class=\"note interactive\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44535-fs-idm20710464\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155837\/trp_operon.png\" width=\"130\" alt=\"QR Code representing a URL\"\/><\/div><p><span id=\"m44535-fs-idm19622064\"> <\/span>Watch <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/trp_operon\" target=\"\">this video<\/a> to learn more about the <span class=\"emphasis\"><em>trp<\/em><\/span> operon.<\/p><\/div><\/div><\/div><div class=\"section\" title=\"Catabolite Activator Protein (CAP): An Activator Regulator\"><div class=\"titlepage\"><div><div><h3 id=\"m44535-fs-idm202194608\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Catabolite Activator Protein (CAP): An Activator Regulator<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44535-fs-idm148740496\"> <\/span>Just as the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is negatively regulated by tryptophan molecules, there are proteins that bind to the operator sequences that act as a <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1634555\"> <\/span>positive regulator<\/em><a id=\"id518375\" class=\"indexterm\"> to turn genes on and activate them. For example, when glucose is scarce, <span class=\"emphasis\"><em>E. coli<\/em><\/span> bacteria can turn to other sugar sources for fuel. To do this, new genes to process these alternate genes must be transcribed. When glucose levels drop, cyclic AMP (cAMP) begins to accumulate in the cell. The cAMP molecule is a signaling molecule that is involved in glucose and energy metabolism in <span class=\"emphasis\"><em>E. coli<\/em><\/span>. When glucose levels decline in the cell, accumulating cAMP binds to the positive regulator <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1643183\"> <\/span>catabolite activator protein (CAP)<\/em><\/a><a id=\"id518404\" class=\"indexterm\">, a protein that binds to the promoters of operons that control the processing of alternative sugars. When cAMP binds to CAP, the complex binds to the promoter region of the genes that are needed to use the alternate sugar sources (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_02\" title=\"Figure&#xA0;16.4.&#xA0;\">Figure\u00a016.4<\/a>). In these operons, a CAP binding site is located upstream of the RNA polymerase binding site in the promoter. This increases the binding ability of RNA polymerase to the promoter region and the transcription of the genes.<\/p><div id=\"m44535-fig-ch16_02_02\" class=\"figure\" title=\"Figure&#xA0;16.4.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44535-fs-idm287484176\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155839\/Figure_16_02_02.jpg\" width=\"450\" alt=\"The lac operon consists of a promoter, an operator, and three genes named lacZ, lacY, and lacA that are located in sequential order on the DNA. In the absence of cAMP, the CAP protein does not bind the DNA. RNA polymerase binds the promoter, and transcription occurs at a slow rate. In the presence of cAMP, a CAP&#x2013;cAMP complex binds to the promoter and increases RNA polymerase activity. As a result, the rate of RNA synthesis is increased.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">When glucose levels fall, <span class=\"emphasis\"><em>E. coli<\/em><\/span> may use other sugars for fuel but must transcribe new genes to do so. As glucose supplies become limited, cAMP levels increase. This cAMP binds to the CAP protein, a positive regulator that binds to an operator region upstream of the genes required to use other sugar sources.<\/div><\/div><\/div><div class=\"section\" title=\"The lac Operon: An Inducer Operon\"><div class=\"titlepage\"><div><div><h3 id=\"m44535-fs-idm146228272\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>lac<\/em><\/span> Operon: An Inducer Operon<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44535-fs-idm17029296\"> <\/span>The third type of gene regulation in prokaryotic cells occurs through <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1276100\"> <\/span>inducible operons<\/em><a id=\"id518497\" class=\"indexterm\">, which have proteins that bind to activate or repress transcription depending on the local environment and the needs of the cell. The <span class=\"emphasis\"><em>lac<\/em><\/span> operon is a typical inducible operon. As mentioned previously, <span class=\"emphasis\"><em>E. coli<\/em><\/span> is able to use other sugars as energy sources when glucose concentrations are low. To do so, the cAMP\u2013CAP protein complex serves as a positive regulator to induce transcription. One such sugar source is lactose. The <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1657851\"> <\/span><span class=\"emphasis\"><em>lac<\/em><\/span> operon<\/em><\/a><a id=\"id518534\" class=\"indexterm\"> encodes the genes necessary to acquire and process the lactose from the local environment. CAP binds to the operator sequence upstream of the promoter that initiates transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon. However, for the <span class=\"emphasis\"><em>lac<\/em><\/span> operon to be activated, two conditions must be met. First, the level of glucose must be very low or non-existent. Second, lactose must be present. Only when glucose is absent and lactose is present will the <span class=\"emphasis\"><em>lac<\/em><\/span> operon be transcribed (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xA0;16.5.&#xA0;\">Figure\u00a016.5<\/a>). This makes sense for the cell, because it would be energetically wasteful to create the proteins to process lactose if glucose was plentiful or lactose was not available.<\/p><div id=\"m44535-fs-idm178239648\" class=\"note art-connection\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Art Connection<\/span><\/div><div class=\"body\"><p><span id=\"m44535-fs-idm151012288\"> <\/span>\n<\/p><div id=\"m44535-fig-ch16_02_03\" class=\"figure\" title=\"Figure&#xA0;16.5.&#xA0;\"><div class=\"body\"><span class=\"inlinemediaobject\"><span id=\"m44535-fs-idm178409184\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155841\/Figure_16_02_03.png\" width=\"300\" alt=\"The lac operon consists of a promoter, an operator, and three genes named lacZ, lacY, and lacA. RNA polymerase binds to the promoter. In the absence of lactose, the lac repressor binds to the operator and prevents RNA polymerase from transcribing the operon. In the presence of lactose, the repressor is released from the operator, and transcription proceeds at a slow rate. Binding of the cAMP&#x2013;CAP complex to the promoter stimulates RNA polymerase activity and increases RNA synthesis. However, even in the presence of the cAMP&#x2013;CAP complex, RNA synthesis is blocked if the repressor binds to the promoter.\"\/><\/span><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">Transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is carefully regulated so that its expression only occurs when glucose is limited and lactose is present to serve as an alternative fuel source.<\/div><\/div><p><span id=\"m44535-fs-idm33204592\"> <\/span>In <span class=\"emphasis\"><em>E. coli<\/em><\/span>, the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is on by default, while the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is off. Why do you think this is the case?<\/p><\/div><\/div><p><span id=\"m44535-fs-idm153663040\"> <\/span>If glucose is absent, then CAP can bind to the operator sequence to activate transcription. If lactose is absent, then the repressor binds to the operator to prevent transcription. If either of these requirements is met, then transcription remains off. Only when both conditions are satisfied is the <span class=\"emphasis\"><em>lac<\/em><\/span> operon transcribed (<a class=\"xref target-table\" href=\"ch16.html#m44535-tab-ch16_02_01\" title=\"Table&#xA0;16.2.&#xA0;\">Table\u00a016.2<\/a>).<\/p><div class=\"table\" id=\"m44535-tab-ch16_02_01\"><table cellpadding=\"0\" style=\"border: 1px solid; border-spacing: 0px;\"><caption><span class=\"cnx-gentext-caption cnx-gentext-t\">Table <\/span><span class=\"cnx-gentext-caption cnx-gentext-n\">16.2. <\/span><\/caption><thead valign=\"bottom\"><tr><th colspan=\"5\" style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">Signals that Induce or Repress Transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> Operon<\/th><\/tr><tr><th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Glucose<\/th><th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">CAP binds<\/th><th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Lactose<\/th><th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Repressor binds<\/th><th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">Transcription<\/th><\/tr><\/thead><tbody valign=\"top\"><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">No<\/td><\/tr><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">Some<\/td><\/tr><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">No<\/td><\/tr><tr><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">+<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">-<\/td><td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 0 !important; text-align: center !important;\">Yes<\/td><\/tr><\/tbody><\/table><\/div><div id=\"m44535-fs-idm116103472\" class=\"note interactive\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44535-fs-idp49045184\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155843\/lac_operon.png\" width=\"120\" alt=\"QR Code representing a URL\"\/><\/div><p><span id=\"m44535-fs-idm187859568\"> <\/span>Watch an <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/lac_operon\" target=\"\">animated tutorial<\/a> about the workings of <span class=\"emphasis\"><em>lac<\/em><\/span> operon here.<\/p><\/div><\/div><\/div><\/div><div xml:lang=\"en\" class=\"section module\" title=\"16.3.&#xA0;Eukaryotic Epigenetic Gene Regulation\"><div class=\"titlepage\"><div><div><h2 id=\"m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<sup><a href=\"co03.html#book-attribution-m44536\">*<\/a><\/sup><\/span><\/span><\/h2><\/div><div class=\"abstract\"><div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"\/><\/span><\/span><\/div><p>By the end of this section, you will be able to:\n<\/p><div class=\"itemizedlist\"><ul class=\"itemizedlist\"><li class=\"listitem\"><p>Explain the process of epigenetic regulation<\/p><\/li><li class=\"listitem\"><p>Describe how access to DNA is controlled by histone modification<\/p><\/li><\/ul><\/div><\/div><\/div><\/div><div class=\"toc\"><ul><li class=\"toc-section\"><a href=\"#m44536-fs-id1896201\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Epigenetic Control: Regulating Access to Genes within the Chromosome<\/span><\/a><\/li><\/ul><\/div><p><span id=\"m44536-fs-id2990488\"> <\/span>Eukaryotic gene expression is more complex than prokaryotic gene expression because the processes of transcription and translation are physically separated. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at many different levels. Eukaryotic gene expression begins with control of access to the DNA. This form of regulation, called epigenetic regulation, occurs even before transcription is initiated.<\/p><div class=\"section\" title=\"Epigenetic Control: Regulating Access to Genes within the Chromosome\"><div class=\"titlepage\"><div><div><h3 id=\"m44536-fs-id1896201\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Epigenetic Control: Regulating Access to Genes within the Chromosome<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44536-fs-id1524776\"> <\/span>The human genome encodes over 20,000 genes; each of the 23 pairs of human chromosomes encodes thousands of genes. The DNA in the nucleus is precisely wound, folded, and compacted into chromosomes so that it will fit into the nucleus. It is also organized so that specific segments can be accessed as needed by a specific cell type.<\/p><p><span id=\"m44536-fs-id2425348\"> <\/span>The first level of organization, or packing, is the winding of DNA strands around histone proteins. Histones package and order DNA into structural units called nucleosome complexes, which can control the access of proteins to the DNA regions (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_01\" title=\"Figure&#xA0;16.6.&#xA0;\">Figure\u00a016.6<\/a><span class=\"bold\"><strong>a<\/strong><\/span>). Under the electron microscope, this winding of DNA around histone proteins to form nucleosomes looks like small beads on a string (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_01\" title=\"Figure&#xA0;16.6.&#xA0;\">Figure\u00a016.6<\/a><span class=\"bold\"><strong>b<\/strong><\/span>). These beads (histone proteins) can move along the string (DNA) and change the structure of the molecule.<\/p><div id=\"m44536-fig-ch16_03_01\" class=\"figure\" title=\"Figure&#xA0;16.6.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44536-fs-id1807369\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155846\/Figure_16_03_01ab.jpg\" width=\"550\" alt=\"Part A depicts a nucleosome composed of spherical histone proteins that are fused together. A double-stranded DNA helix wraps around the nucleosome twice. Free DNA extends from either end of the nucleosome. Part B is an electron micrograph of DNA that is associated with nucleosomes. Each nucleosome looks like a bead. The beads are connected together by free DNA. Nine beads strung together is approximately 150 nm across.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">DNA is folded around histone proteins to create (a) nucleosome complexes. These nucleosomes control the access of proteins to the underlying DNA. When viewed through an electron microscope (b), the nucleosomes look like beads on a string. (credit \u201cmicrograph\u201d: modification of work by Chris Woodcock)<\/div><\/div><p><span id=\"m44536-fs-id1596128\"> <\/span>If DNA encoding a specific gene is to be transcribed into RNA, the nucleosomes surrounding that region of DNA can slide down the DNA to open that specific chromosomal region and allow for the transcriptional machinery (RNA polymerase) to initiate transcription (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xA0;16.7.&#xA0;\">Figure\u00a016.7<\/a>). Nucleosomes can move to open the chromosome structure to expose a segment of DNA, but do so in a very controlled manner.<\/p><div id=\"m44536-fs-id1485526\" class=\"note art-connection\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Art Connection<\/span><\/div><div class=\"body\"><p><span id=\"m44536-fs-id2020475\"> <\/span><\/p><div id=\"m44536-fig-ch16_03_02\" class=\"figure\" title=\"Figure&#xA0;16.7.&#xA0;\"><div class=\"body\"><span class=\"inlinemediaobject\"><span id=\"m44536-fs-id3078242\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155848\/Figure_16_03_02.png\" width=\"450\" alt=\"Nucleosomes are depicted as wheel-like structures. The nucleosomes are made up of histones, and have DNA wrapped around the outside. Each histone has a tail that juts out from the wheel. When DNA and the histone tails are methylated, the nucleosomes pack tightly together so there is no free DNA. Transcription factors cannot bind, and genes are not expressed. Acetylation of histone tails results in a looser packing of the nucleosomes. Free DNA is exposed between the nucleosomes, and transcription factors are able to bind genes on this exposed DNA.\"\/><\/span><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">Nucleosomes can slide along DNA. When nucleosomes are spaced closely together (top), transcription factors cannot bind and gene expression is turned off. When the nucleosomes are spaced far apart (bottom), the DNA is exposed. Transcription factors can bind, allowing gene expression to occur. Modifications to the histones and DNA affect nucleosome spacing.<\/div><\/div><p><span id=\"m44536-fs-id1236637\"> <\/span>In females, one of the two X chromosomes is inactivated during embryonic development because of epigenetic changes to the chromatin. What impact do you think these changes would have on nucleosome packing?<\/p><\/div><\/div><p><span id=\"m44536-fs-id1509913\"> <\/span>How the histone proteins move is dependent on signals found on both the histone proteins and on the DNA. These signals are tags added to histone proteins and DNA that tell the histones if a chromosomal region should be open or closed (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_03\" title=\"Figure&#xA0;16.8.&#xA0;\">Figure\u00a016.8<\/a> depicts modifications to histone proteins and DNA). These tags are not permanent, but may be added or removed as needed. They are chemical modifications (phosphate, methyl, or acetyl groups) that are attached to specific amino acids in the protein or to the nucleotides of the DNA. The tags do not alter the DNA base sequence, but they do alter how tightly wound the DNA is around the histone proteins. DNA is a negatively charged molecule; therefore, changes in the charge of the histone will change how tightly wound the DNA molecule will be. When unmodified, the histone proteins have a large positive charge; by adding chemical modifications like acetyl groups, the charge becomes less positive.<\/p><p><span id=\"m44536-fs-id2261473\"> <\/span>The DNA molecule itself can also be modified. This occurs within very specific regions called CpG islands. These are stretches with a high frequency of cytosine and guanine dinucleotide DNA pairs (CG) found in the promoter regions of genes. When this configuration exists, the cytosine member of the pair can be methylated (a methyl group is added). This modification changes how the DNA interacts with proteins, including the histone proteins that control access to the region. Highly methylated (hypermethylated) DNA regions with deacetylated histones are tightly coiled and transcriptionally inactive.<\/p><div id=\"m44536-fig-ch16_03_03\" class=\"figure\" title=\"Figure&#xA0;16.8.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44536-fs-id2322545\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155850\/Figure_16_03_03.jpg\" width=\"500\" alt=\"Illustration shows a chromosome that is partially unraveled and magnified, revealing histone proteins wound around the DNA double helix. Histones are proteins around which DNA winds for compaction and gene regulation. Methylation of DNA and chemical modification of histone tails are known as epigenetic changes. Epigenetic changes alter the spacing of nucleosomes and change gene expression. Epigenetic changes may result from development, either in utero or in childhood, environmental chemicals, drugs, aging, or diet. Epigenetic changes may result in cancer, autoimmune disease, mental disorders, and diabetes.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.8<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">Histone proteins and DNA nucleotides can be modified chemically. Modifications affect nucleosome spacing and gene expression. (credit: modification of work by NIH)<\/div><\/div><p><span id=\"m44536-fs-id1605467\"> <\/span>This type of gene regulation is called epigenetic regulation. Epigenetic means \u201caround genetics.\u201d The changes that occur to the histone proteins and DNA do not alter the nucleotide sequence and are not permanent. Instead, these changes are temporary (although they often persist through multiple rounds of cell division) and alter the chromosomal structure (open or closed) as needed. A gene can be turned on or off depending upon the location and modifications to the histone proteins and DNA. If a gene is to be transcribed, the histone proteins and DNA are modified surrounding the chromosomal region encoding that gene. This opens the chromosomal region to allow access for RNA polymerase and other proteins, called <em class=\"glossterm\"><span id=\"m44536-autoid-cnx2dbk-id1513751\"> <\/span>transcription factors<\/em><a id=\"id424527\" class=\"indexterm\">, to bind to the promoter region, located just upstream of the gene, and initiate transcription. If a gene is to remain turned off, or silenced, the histone proteins and DNA have different modifications that signal a closed chromosomal configuration. In this closed configuration, the RNA polymerase and transcription factors do not have access to the DNA and transcription cannot occur (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xA0;16.7.&#xA0;\">Figure\u00a016.7<\/a>).<\/p><div id=\"m44536-fs-id1469378\" class=\"note interactive\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44536-fs-id3096241\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155854\/epigenetic_reg.png\" width=\"120\" alt=\"QR Code representing a URL\"\/><\/div><p><span id=\"m44536-fs-id1724210\"> <\/span>View <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/epigenetic_reg\" target=\"\">this video<\/a> that describes how epigenetic regulation controls gene expression.<\/p><\/div><\/div><\/div><\/div><div xml:lang=\"en\" class=\"section module\" title=\"16.4.&#xA0;Eukaryotic Transcription Gene Regulation\"><div class=\"titlepage\"><div><div><h2 id=\"m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<sup><a href=\"co03.html#book-attribution-m44538\">*<\/a><\/sup><\/span><\/span><\/h2><\/div><div class=\"abstract\"><div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"\/><\/span><\/span><\/div><p>By the end of this section, you will be able to:\n<\/p><div class=\"itemizedlist\"><ul class=\"itemizedlist\"><li class=\"listitem\"><p>Discuss the role of transcription factors in gene regulation<\/p><\/li><li class=\"listitem\"><p>Explain how enhancers and repressors regulate gene expression<\/p><\/li><\/ul><\/div><\/div><\/div><\/div><div class=\"toc\"><ul><li class=\"toc-section\"><a href=\"#m44538-fs-id1967852\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Promoter and the Transcription Machinery<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44538-fs-id2571418\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Enhancers and Transcription<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44538-fs-id685962\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Turning Genes Off: Transcriptional Repressors<\/span><\/a><\/li><\/ul><\/div><p><span id=\"m44538-fs-id2745728\"> <\/span>Like prokaryotic cells, the transcription of genes in eukaryotes requires the actions of an RNA polymerase to bind to a sequence upstream of a gene to initiate transcription. However, unlike prokaryotic cells, the eukaryotic RNA polymerase requires other proteins, or transcription factors, to facilitate transcription initiation. Transcription factors are proteins that bind to the promoter sequence and other regulatory sequences to control the transcription of the target gene. RNA polymerase by itself cannot initiate transcription in eukaryotic cells. Transcription factors must bind to the promoter region first and recruit RNA polymerase to the site for transcription to be established.<\/p><div id=\"m44538-fs-id2022629\" class=\"note interactive\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44538-fs-id1595515\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155857\/transcript_RNA.png\" width=\"120\" alt=\"QR Code representing a URL\"\/><\/div><p><span id=\"m44538-fs-id2192558\"> <\/span>View the process of transcription\u2014the making of RNA from a DNA template\u2014at <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/transcript_RNA\" target=\"\">this site<\/a>.<\/p><\/div><\/div><div class=\"section\" title=\"The Promoter and the Transcription Machinery\"><div class=\"titlepage\"><div><div><h3 id=\"m44538-fs-id1967852\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Promoter and the Transcription Machinery<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44538-fs-id1645226\"> <\/span>Genes are organized to make the control of gene expression easier. The promoter region is immediately upstream of the coding sequence. This region can be short (only a few nucleotides in length) or quite long (hundreds of nucleotides long). The longer the promoter, the more available space for proteins to bind. This also adds more control to the transcription process. The length of the promoter is gene-specific and can differ dramatically between genes. Consequently, the level of control of gene expression can also differ quite dramatically between genes. The purpose of the promoter is to bind transcription factors that control the initiation of transcription.<\/p><p><span id=\"m44538-fs-id2904783\"> <\/span>Within the promoter region, just upstream of the transcriptional start site, resides the TATA box. This box is simply a repeat of thymine and adenine dinucleotides (literally, TATA repeats). RNA polymerase binds to the transcription initiation complex, allowing transcription to occur. To initiate transcription, a transcription factor (TFIID) is the first to bind to the TATA box. Binding of TFIID recruits other transcription factors, including TFIIB, TFIIE, TFIIF, and TFIIH to the TATA box. Once this complex is assembled, RNA polymerase can bind to its upstream sequence. When bound along with the transcription factors, RNA polymerase is phosphorylated. This releases part of the protein from the DNA to activate the transcription initiation complex and places RNA polymerase in the correct orientation to begin transcription; DNA-bending protein brings the enhancer, which can be quite a distance from the gene, in contact with transcription factors and mediator proteins (<a class=\"xref target-figure\" href=\"ch16.html#m44538-fig-ch16_04_01\" title=\"Figure&#xA0;16.9.&#xA0;\">Figure\u00a016.9<\/a>).<\/p><div id=\"m44538-fig-ch16_04_01\" class=\"figure\" title=\"Figure&#xA0;16.9.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44538-fs-id1778252\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155900\/Figure_16_04_01.jpg\" width=\"320\" alt=\"Eukaryotic gene expression is controlled by a promoter immediately adjacent to the gene, and an enhancer far upstream. The DNA folds over itself, bringing the enhancer next to the promoter. Transcription factors and mediator proteins are sandwiched between the promoter and the enhancer. Short DNA sequences within the enhancer called distal control elements bind activators, which in turn bind transcription factors and mediator proteins bound to the promoter. RNA polymerase binds the complex, allowing transcription to begin. Different genes have enhancers with different distal control elements, allowing differential regulation of transcription.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.9<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">An enhancer is a DNA sequence that promotes transcription. Each enhancer is made up of short DNA sequences called distal control elements. Activators bound to the distal control elements interact with mediator proteins and transcription factors. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.<\/div><\/div><p><span id=\"m44538-fs-id1911410\"> <\/span>In addition to the general transcription factors, other transcription factors can bind to the promoter to regulate gene transcription. These transcription factors bind to the promoters of a specific set of genes. They are not general transcription factors that bind to every promoter complex, but are recruited to a specific sequence on the promoter of a specific gene. There are hundreds of transcription factors in a cell that each bind specifically to a particular DNA sequence motif. When transcription factors bind to the promoter just upstream of the encoded gene, it is referred to as a <em class=\"glossterm\"><span id=\"m44538-autoid-cnx2dbk-id1466670\"> <\/span><span class=\"emphasis\"><em>cis<\/em><\/span>-acting element<\/em><a id=\"id519492\" class=\"indexterm\">, because it is on the same chromosome just next to the gene. The region that a particular transcription factor binds to is called the <em class=\"glossterm\"><span id=\"m44538-autoid-cnx2dbk-id1394712\"> <\/span>transcription factor binding site<\/em><\/a><a id=\"id519508\" class=\"indexterm\">. Transcription factors respond to environmental stimuli that cause the proteins to find their binding sites and initiate transcription of the gene that is needed.<\/a><\/p><\/div><div class=\"section\" title=\"Enhancers and Transcription\"><div class=\"titlepage\"><div><div><h3 id=\"m44538-fs-id2571418\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Enhancers and Transcription<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44538-fs-id2700899\"> <\/span>In some eukaryotic genes, there are regions that help increase or enhance transcription. These regions, called <em class=\"glossterm\"><span id=\"m44538-autoid-cnx2dbk-id1394731\"> <\/span>enhancers<\/em><a id=\"id519533\" class=\"indexterm\">, are not necessarily close to the genes they enhance. They can be located upstream of a gene, within the coding region of the gene, downstream of a gene, or may be thousands of nucleotides away.<\/a><\/p><p><span id=\"m44538-fs-id2373880\"> <\/span>Enhancer regions are binding sequences, or sites, for transcription factors. When a DNA-bending protein binds, the shape of the DNA changes (<a class=\"xref target-figure\" href=\"ch16.html#m44538-fig-ch16_04_01\" title=\"Figure&#xA0;16.9.&#xA0;\">Figure\u00a016.9<\/a>). This shape change allows for the interaction of the activators bound to the enhancers with the transcription factors bound to the promoter region and the RNA polymerase. Whereas DNA is generally depicted as a straight line in two dimensions, it is actually a three-dimensional object. Therefore, a nucleotide sequence thousands of nucleotides away can fold over and interact with a specific promoter.<\/p><\/div><div class=\"section\" title=\"Turning Genes Off: Transcriptional Repressors\"><div class=\"titlepage\"><div><div><h3 id=\"m44538-fs-id685962\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Turning Genes Off: Transcriptional Repressors<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44538-fs-id1797856\"> <\/span>Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli to prevent the binding of activating transcription factors.<\/p><\/div><\/div><div xml:lang=\"en\" class=\"section module\" title=\"16.5.&#xA0;Eukaryotic Post-transcriptional Gene Regulation\"><div class=\"titlepage\"><div><div><h2 id=\"m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<sup><a href=\"co03.html#book-attribution-m44539\">*<\/a><\/sup><\/span><\/span><\/h2><\/div><div class=\"abstract\"><div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"\/><\/span><\/span><\/div><p>By the end of this section, you will be able to:\n<\/p><div class=\"itemizedlist\"><ul class=\"itemizedlist\"><li class=\"listitem\"><p>Understand RNA splicing and explain its role in regulating gene expression<\/p><\/li><li class=\"listitem\"><p>Describe the importance of RNA stability in gene regulation<\/p><\/li><\/ul><\/div><\/div><\/div><\/div><div class=\"toc\"><ul><li class=\"toc-section\"><a href=\"#m44539-fs-id2019050\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA splicing, the first stage of post-transcriptional control<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44539-fs-id3071072\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Control of RNA Stability<\/span><\/a><ul><li class=\"toc-section\"><a href=\"#m44539-fs-id2590621\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA Stability and microRNAs<\/span><\/a><\/li><\/ul><\/li><\/ul><\/div><p><span id=\"m44539-fs-id2098364\"> <\/span>RNA is transcribed, but must be processed into a mature form before translation can begin. This processing after an RNA molecule has been transcribed, but before it is translated into a protein, is called post-transcriptional modification. As with the epigenetic and transcriptional stages of processing, this post-transcriptional step can also be regulated to control gene expression in the cell. If the RNA is not processed, shuttled, or translated, then no protein will be synthesized.<\/p><div class=\"section\" title=\"RNA splicing, the first stage of post-transcriptional control\"><div class=\"titlepage\"><div><div><h3 id=\"m44539-fs-id2019050\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA splicing, the first stage of post-transcriptional control<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44539-fs-id1899262\"> <\/span>In eukaryotic cells, the RNA transcript often contains regions, called introns, that are removed prior to translation. The regions of RNA that code for protein are called exons (<a class=\"xref target-figure\" href=\"ch16.html#m44539-fig-ch16_05_01\" title=\"Figure&#xA0;16.10.&#xA0;\">Figure\u00a016.10<\/a>). After an RNA molecule has been transcribed, but prior to its departure from the nucleus to be translated, the RNA is processed and the introns are removed by splicing.<\/p><div id=\"m44539-fig-ch16_05_01\" class=\"figure\" title=\"Figure&#xA0;16.10.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44539-fs-id1770169\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155902\/Figure_16_05_03.jpg\" width=\"400\" alt=\"A pre-mRNA has four exons separated by three introns. The pre-mRNA can be alternatively spliced to create two different proteins, each with three exons. One protein contains exons one, two, and three. The other protein contains exons one, three and four.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.10<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">Pre-mRNA can be alternatively spliced to create different proteins.<\/div><\/div><div id=\"m44539-fs-id2048195\" class=\"note evolution\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Evolution Connection<\/span><\/div><div class=\"body\"><p title=\"Alternative RNA Splicing\"><span id=\"m44539-fs-id1418200\"> <\/span><\/p><div class=\"title\"><b>Alternative RNA Splicing<\/b><\/div><p title=\"Alternative RNA Splicing\">In the 1970s, genes were first observed that exhibited alternative RNA splicing. Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of introns, and sometimes exons, are removed from the transcript (<a class=\"xref target-figure\" href=\"ch16.html#m44539-fig-ch16_05_02\" title=\"Figure&#xA0;16.11.&#xA0;\">Figure\u00a016.11<\/a>). This alternative splicing can be haphazard, but more often it is controlled and acts as a mechanism of gene regulation, with the frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development. Alternative splicing is now understood to be a common mechanism of gene regulation in eukaryotes; according to one estimate, 70 percent of genes in humans are expressed as multiple proteins through alternative splicing.<\/p><div id=\"m44539-fig-ch16_05_02\" class=\"figure\" title=\"Figure&#xA0;16.11.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44539-fs-id2194968\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155905\/Figure_15_04_02.jpg\" width=\"400\" alt=\"Diagram shows five methods of alternative splicing of pre-mRNA. When exon skipping occurs, an exon is spliced out in one mature mRNA product and retained in another. When mutually exclusive exons are present in the pre-mRNA, only one is retained in the mature mRNA. When an alternative 5&#x2019; donor site is present, the location of the 5&#x2019; splice site is variable. When an alternative 3&#x2019; acceptor site is present, the location of the 3&#x2019; splice site is variable. Intron retention results in an intron being retained in one mature mRNA and spliced out in another.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.11<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">There are five basic modes of alternative splicing.<\/div><\/div><p><span id=\"m44539-fs-id1770543\"> <\/span>How could alternative splicing evolve? Introns have a beginning and ending recognition sequence; it is easy to imagine the failure of the splicing mechanism to identify the end of an intron and instead find the end of the next intron, thus removing two introns and the intervening exon. In fact, there are mechanisms in place to prevent such intron skipping, but mutations are likely to lead to their failure. Such \u201cmistakes\u201d would more than likely produce a nonfunctional protein. Indeed, the cause of many genetic diseases is alternative splicing rather than mutations in a sequence. However, alternative splicing would create a protein variant without the loss of the original protein, opening up possibilities for adaptation of the new variant to new functions. Gene duplication has played an important role in the evolution of new functions in a similar way by providing genes that may evolve without eliminating the original, functional protein.<\/p><\/div><\/div><div id=\"m44539-fs-id2030028\" class=\"note interactive\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44539-fs-id2004529\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155908\/mRNA_splicing.png\" width=\"120\" alt=\"QR Code representing a URL\"\/><\/div><p><span id=\"m44539-fs-id2571418\"> <\/span>Visualize how mRNA splicing happens by watching the process in action in <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/mRNA_splicing\" target=\"\">this video<\/a>.<\/p><\/div><\/div><\/div><div class=\"section\" title=\"Control of RNA Stability\"><div class=\"titlepage\"><div><div><h3 id=\"m44539-fs-id3071072\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Control of RNA Stability<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44539-fs-id1703747\"> <\/span>Before the mRNA leaves the nucleus, it is given two protective \"caps\" that prevent the end of the strand from degrading during its journey. The <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578035\"> <\/span>5' cap<\/em><a id=\"id520137\" class=\"indexterm\">, which is placed on the 5' end of the mRNA, is usually composed of a methylated guanosine triphosphate molecule (GTP). The  <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578040\"> <\/span>poly-A tail<\/em><\/a><a id=\"id520148\" class=\"indexterm\">, which is attached to the 3' end, is usually composed of a series of adenine nucleotides. Once the RNA is transported to the cytoplasm, the length of time that the RNA resides there can be controlled. Each RNA molecule has a defined lifespan and decays at a specific rate. This rate of decay can influence how much protein is in the cell. If the decay rate is increased, the RNA will not exist in the cytoplasm as long, shortening the time for translation to occur. Conversely, if the rate of decay is decreased, the RNA molecule will reside in the cytoplasm longer and more protein can be translated. This rate of decay is referred to as the RNA stability. If the RNA is stable, it will be detected for longer periods of time in the cytoplasm.<\/a><\/p><p><span id=\"m44539-fs-id2167834\"> <\/span>Binding of proteins to the RNA can influence its stability. Proteins, called <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578056\"> <\/span>RNA-binding proteins<\/em><a id=\"id520170\" class=\"indexterm\">, or RBPs, can bind to the regions of the RNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578061\"> <\/span>untranslated regions<\/em><\/a><a id=\"id520182\" class=\"indexterm\">, or UTRs. They are not introns (those have been removed in the nucleus). Rather, these are regions that regulate mRNA localization, stability, and protein translation. The region just before the protein-coding region is called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578067\"> <\/span>5' UTR<\/em><\/a><a id=\"id520194\" class=\"indexterm\">, whereas the region after the coding region is called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578070\"> <\/span>3' UTR<\/em><\/a><a id=\"id520206\" class=\"indexterm\"> (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44539-fig-ch16_05_03\" title=\"Figure&#xA0;16.12.&#xA0;\">Figure\u00a016.12<\/a>). The binding of RBPs to these regions can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.<\/p><div id=\"m44539-fig-ch16_05_03\" class=\"figure\" title=\"Figure&#xA0;16.12.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44539-fs-id1445473\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155910\/Figure_16_05_02.jpg\" width=\"450\" alt=\"In the mature RNA molecule, exons are spliced together between the 5' and 3' untranslated regions. A 5' cap is attached to the 5' untranslated region, and a poly-A tail is attached to the 3' untranslated region. RNA-binding proteins associate with the 5' and 3' untranslated regions.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.12<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">The protein-coding region of mRNA is flanked by 5' and 3' untranslated regions (UTRs). The presence of RNA-binding proteins at the 5' or 3' UTR influences the stability of the RNA molecule.<\/div><\/div><div class=\"section\" title=\"RNA Stability and microRNAs\"><div class=\"titlepage\"><div><div><h4 id=\"m44539-fs-id2590621\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA Stability and microRNAs<\/span><\/span><\/h4><\/div><\/div><\/div><p><span id=\"m44539-fs-id1550134\"> <\/span>In addition to RBPs that bind to and control (increase or decrease) RNA stability, other elements called microRNAs can bind to the RNA molecule. These <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1598074\"> <\/span>microRNAs<\/em><a id=\"id520265\" class=\"indexterm\">, or miRNAs, are short RNA molecules that are only 21\u201324 nucleotides in length. The miRNAs are made in the nucleus as longer pre-miRNAs. These pre-miRNAs are chopped into mature miRNAs by a protein called <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1624188\"> <\/span>dicer<\/em><\/a><a id=\"id520280\" class=\"indexterm\">. Like transcription factors and RBPs, mature miRNAs recognize a specific sequence and bind to the RNA; however, miRNAs also associate with a ribonucleoprotein complex called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1624193\"> <\/span>RNA-induced silencing complex (RISC)<\/em><\/a><a id=\"id520292\" class=\"indexterm\">. RISC binds along with the miRNA to degrade the target mRNA. Together, miRNAs and the RISC complex rapidly destroy the RNA molecule.<\/a><\/p><\/div><\/div><\/div><div xml:lang=\"en\" class=\"section module\" title=\"16.6.&#xA0;Eukaryotic Translational and Post-translational Gene Regulation\"><div class=\"titlepage\"><div><div><h2 id=\"m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<sup><a href=\"co03.html#book-attribution-m44542\">*<\/a><\/sup><\/span><\/span><\/h2><\/div><div class=\"abstract\"><div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"\/><\/span><\/span><\/div><p>By the end of this section, you will be able to:\n<\/p><div class=\"itemizedlist\"><ul class=\"itemizedlist\"><li class=\"listitem\"><p>Understand the process of translation and discuss its key factors<\/p><\/li><li class=\"listitem\"><p>Describe how the initiation complex controls translation<\/p><\/li><li class=\"listitem\"><p>Explain the different ways in which the post-translational control of gene expression takes place<\/p><\/li><\/ul><\/div><\/div><\/div><\/div><div class=\"toc\"><ul><li class=\"toc-section\"><a href=\"#m44542-fs-id1396738\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Initiation Complex and Translation Rate<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44542-fs-id1956507\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Chemical Modifications, Protein Activity, and Longevity<\/span><\/a><\/li><\/ul><\/div><p><span id=\"m44542-fs-id1976887\"> <\/span>After the RNA has been transported to the cytoplasm, it is translated into protein. Control of this process is largely dependent on the RNA molecule. As previously discussed, the stability of the RNA will have a large impact on its translation into a protein. As the stability changes, the amount of time that it is available for translation also changes.<\/p><div class=\"section\" title=\"The Initiation Complex and Translation Rate\"><div class=\"titlepage\"><div><div><h3 id=\"m44542-fs-id1396738\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Initiation Complex and Translation Rate<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44542-fs-id2754887\"> <\/span>Like transcription, translation is controlled by proteins that bind and initiate the process. In translation, the complex that assembles to start the process is referred to as the <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302722\"> <\/span>initiation complex<\/em><a id=\"id520685\" class=\"indexterm\">. The first protein to bind to the RNA to initiate translation is the <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302725\"> <\/span>eukaryotic initiation factor-2 (eIF-2)<\/em><\/a><a id=\"id520696\" class=\"indexterm\">. The eIF-2 protein is active when it binds to the high-energy molecule <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302729\"> <\/span>guanosine triphosphate (GTP)<\/em><\/a><a id=\"id520707\" class=\"indexterm\">. GTP provides the energy to start the reaction by giving up a phosphate and becoming <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302733\"> <\/span>guanosine diphosphate (GDP)<\/em><\/a><a id=\"id520718\" class=\"indexterm\">. The eIF-2 protein bound to GTP binds to the small <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302737\"> <\/span>40S ribosomal subunit<\/em><\/a><a id=\"id520728\" class=\"indexterm\">. When bound, the methionine initiator tRNA associates with the eIF-2\/40S ribosome complex, bringing along with it the mRNA to be translated. At this point, when the initiator complex is assembled, the GTP is converted into GDP and energy is released. The phosphate and the eIF-2 protein are released from the complex and the large <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302743\"> <\/span>60S ribosomal subunit<\/em><\/a><a id=\"id520742\" class=\"indexterm\"> binds to translate the RNA. The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly and translation is impeded (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xA0;16.13.&#xA0;\">Figure\u00a016.13<\/a>). When eIF-2 remains unphosphorylated, it binds the RNA and actively translates the protein.<\/p><div id=\"m44542-fs-id2339240\" class=\"note art-connection\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Art Connection<\/span><\/div><div class=\"body\"><p><span id=\"m44542-fs-id2250537\"> <\/span>\n<\/p><div id=\"m44542-fig-ch16_06_01\" class=\"figure\" title=\"Figure&#xA0;16.13.&#xA0;\"><div class=\"body\"><span class=\"inlinemediaobject\"><span id=\"m44542-fs-id1453957\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155913\/Figure_16_06_01.png\" width=\"320\" alt=\"The eIF2 protein is a translation factor that binds to the small 40S ribosome subunit. When eIF2 is phosphorylated, translation is blocked.\"\/><\/span><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.13<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">Gene expression can be controlled by factors that bind the translation initiation complex.<\/div><\/div><p><span id=\"m44542-fs-id1770367\"> <\/span>An increase in phosphorylation levels of eIF-2 has been observed in patients with neurodegenerative diseases such as Alzheimer\u2019s, Parkinson\u2019s, and Huntington\u2019s. What impact do you think this might have on protein synthesis?<\/p><\/div><\/div><\/div><div class=\"section\" title=\"Chemical Modifications, Protein Activity, and Longevity\"><div class=\"titlepage\"><div><div><h3 id=\"m44542-fs-id1956507\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Chemical Modifications, Protein Activity, and Longevity<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44542-fs-id3321766\"> <\/span>Proteins can be chemically modified with the addition of groups including methyl, phosphate, acetyl, and ubiquitin groups. The addition or removal of these groups from proteins regulates their activity or the length of time they exist in the cell. Sometimes these modifications can regulate where a protein is found in the cell\u2014for example, in the nucleus, the cytoplasm, or attached to the plasma membrane.<\/p><p><span id=\"m44542-fs-id2080792\"> <\/span>Chemical modifications occur in response to external stimuli such as stress, the lack of nutrients, heat, or ultraviolet light exposure. These changes can alter epigenetic accessibility, transcription, mRNA stability, or translation\u2014all resulting in changes in expression of various genes. This is an efficient way for the cell to rapidly change the levels of specific proteins in response to the environment.  Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).<\/p><p><span id=\"m44542-fs-id3327902\"> <\/span> The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1421910\"> <\/span>proteasome<\/em><a id=\"id520859\" class=\"indexterm\">, an organelle that functions to remove proteins, to be degraded (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_02\" title=\"Figure&#xA0;16.14.&#xA0;\">Figure\u00a016.14<\/a>). One way to control gene expression, therefore, is to alter the longevity of the protein.<\/p><div id=\"m44542-fig-ch16_06_02\" class=\"figure\" title=\"Figure&#xA0;16.14.&#xA0;\"><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44542-fs-id2304651\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155916\/Figure_16_06_02.jpg\" width=\"350\" alt=\"Multiple ubiquitin groups bind to a protein. The tagged protein is then fed into the hollow tube of a proteasome. The proteasome degrades the protein.\"\/><\/div><\/div><div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.14<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"\/><\/div><div class=\"caption\">Proteins with ubiquitin tags are marked for degradation within the proteasome.<\/div><\/div><\/div><\/div><div xml:lang=\"en\" class=\"section module\" title=\"16.7.&#xA0;Cancer and Gene Regulation\"><div class=\"titlepage\"><div><div><h2 id=\"m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<sup><a href=\"co03.html#book-attribution-m44548\">*<\/a><\/sup><\/span><\/span><\/h2><\/div><div class=\"abstract\"><div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"\/><\/span><\/span><\/div><p>By the end of this section, you will be able to:\n<\/p><div class=\"itemizedlist\"><ul class=\"itemizedlist\"><li class=\"listitem\"><p>Describe how changes to gene expression can cause cancer<\/p><\/li><li class=\"listitem\"><p>Explain how changes to gene expression at different levels can disrupt the cell cycle<\/p><\/li><li class=\"listitem\"><p>Discuss how understanding regulation of gene expression can lead to better drug design<\/p><\/li><\/ul><\/div><\/div><\/div><\/div><div class=\"toc\"><ul><li class=\"toc-section\"><a href=\"#m44548-fs-id1775261\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer: Disease of Altered Gene Expression<\/span><\/a><ul><li class=\"toc-section\"><a href=\"#m44548-fs-id1787656\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Tumor Suppressor Genes, Oncogenes, and Cancer<\/span><\/a><\/li><\/ul><\/li><li class=\"toc-section\"><a href=\"#m44548-fs-id2570388\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Epigenetic Alterations<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44548-fs-id1977751\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Transcriptional Control<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44548-fs-id2749879\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Post-transcriptional Control<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44548-fs-id1988417\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Translational\/Post-translational Control<\/span><\/a><\/li><li class=\"toc-section\"><a href=\"#m44548-fs-idp254559760\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">New Drugs to Combat Cancer: Targeted Therapies<\/span><\/a><\/li><\/ul><\/div><p><span id=\"m44548-fs-id2905050\"> <\/span>Cancer is not a single disease but includes many different diseases.  In cancer cells, mutations modify cell-cycle control and cells don\u2019t stop growing as they normally would. Mutations can also alter the growth rate or the progression of the cell through the cell cycle. One example of a gene modification that alters the growth rate is increased phosphorylation of cyclin B, a protein that controls the progression of a cell through the cell cycle and serves as a cell-cycle checkpoint protein.<\/p><p><span id=\"m44548-fs-id2337886\"> <\/span>For cells to move through each phase of the cell cycle, the cell must pass through checkpoints. This ensures that the cell has properly completed the step and has not encountered any mutation that will alter its function. Many proteins, including cyclin B, control these checkpoints. The phosphorylation of cyclin B, a post-translational event, alters its function. As a result, cells can progress through the cell cycle unimpeded, even if mutations exist in the cell and its growth should be terminated. This post-translational change of cyclin B prevents it from controlling the cell cycle and contributes to the development of cancer.<\/p><div class=\"section\" title=\"Cancer: Disease of Altered Gene Expression\"><div class=\"titlepage\"><div><div><h3 id=\"m44548-fs-id1775261\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer: Disease of Altered Gene Expression<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44548-fs-id1772073\"> <\/span>Cancer can be described as a disease of altered gene expression. There are many proteins that are turned on or off (gene activation or gene silencing) that dramatically alter the overall activity of the cell. A gene that is not normally expressed in that cell can be switched on and expressed at high levels. This can be the result of gene mutation or changes in gene regulation (epigenetic, transcription, post-transcription, translation, or post-translation).<\/p><p><span id=\"m44548-fs-id1568624\"> <\/span>Changes in epigenetic regulation, transcription, RNA stability, protein translation, and post-translational control can be detected in cancer. While these changes don\u2019t occur simultaneously in one cancer, changes at each of these levels can be detected when observing cancer at different sites in different individuals. Therefore, changes in <em class=\"glossterm\"><span id=\"m44548-autoid-cnx2dbk-id1414218\"> <\/span>histone acetylation<\/em><a id=\"id521318\" class=\"indexterm\"> (epigenetic modification that leads to gene silencing), activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification can all be detected at some point in various cancer cells. Scientists are working to understand the common changes that give rise to certain types of cancer or how a modification might be exploited to destroy a tumor cell.<\/a><\/p><div class=\"section\" title=\"Tumor Suppressor Genes, Oncogenes, and Cancer\"><div class=\"titlepage\"><div><div><h4 id=\"m44548-fs-id1787656\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Tumor Suppressor Genes, Oncogenes, and Cancer<\/span><\/span><\/h4><\/div><\/div><\/div><p><span id=\"m44548-fs-id1524784\"> <\/span>In normal cells, some genes function to prevent excess, inappropriate cell growth. These are tumor suppressor genes, which are active in normal cells to prevent uncontrolled cell growth. There are many tumor suppressor genes in cells. The most studied tumor suppressor gene is p53, which is mutated in over 50 percent of all cancer types.  The p53 protein itself functions as a transcription factor. It can bind to sites in the promoters of genes to initiate transcription. Therefore, the mutation of p53 in cancer will dramatically alter the transcriptional activity of its target genes.<\/p><div id=\"m44548-fs-id1687530\" class=\"note interactive\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div><div class=\"body\"><div class=\"mediaobject\"><span id=\"m44548-fs-id2334394\"> <\/span><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155919\/p53_cancer.png\" width=\"120\" alt=\"QR Code representing a URL\"\/><\/div><p><span id=\"m44548-fs-id2126300\"> <\/span>Watch <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/p53_cancer\" target=\"\">this animation<\/a> to learn more about the use of p53 in fighting cancer.<\/p><\/div><\/div><p><span id=\"m44548-fs-id1461234\"> <\/span>Proto-oncogenes are positive cell-cycle regulators. When mutated, proto-oncogenes can become oncogenes and cause cancer. Overexpression of the oncogene can lead to uncontrolled cell growth. This is because oncogenes can alter transcriptional activity, stability, or protein translation of another gene that directly or indirectly controls cell growth. An example of an oncogene involved in cancer is a protein called myc. <em class=\"glossterm\"><span id=\"m44548-autoid-cnx2dbk-id1439919\"> <\/span>Myc<\/em><a id=\"id521401\" class=\"indexterm\"> is a transcription factor that is aberrantly activated in Burkett\u2019s Lymphoma, a cancer of the lymph system. Overexpression of myc transforms normal B cells into cancerous cells that continue to grow uncontrollably. High B-cell numbers can result in tumors that can interfere with normal bodily function. Patients with Burkett\u2019s lymphoma can develop tumors on their jaw or in their mouth that interfere with the ability to eat.<\/a><\/p><\/div><\/div><div class=\"section\" title=\"Cancer and Epigenetic Alterations\"><div class=\"titlepage\"><div><div><h3 id=\"m44548-fs-id2570388\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Epigenetic Alterations<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44548-fs-id1675964\"> <\/span>Silencing genes through epigenetic mechanisms is also very common in cancer cells. There are characteristic modifications to histone proteins and DNA that are associated with silenced genes. In cancer cells, the DNA in the promoter region of silenced genes is methylated on cytosine DNA residues in CpG islands. Histone proteins that surround that region lack the acetylation modification that is present when the genes are expressed in normal cells. This combination of DNA methylation and histone deacetylation (epigenetic modifications that lead to gene silencing) is commonly found in cancer. When these modifications occur, the gene present in that chromosomal region is silenced. Increasingly, scientists understand how epigenetic changes are altered in cancer. Because these changes are temporary and can be reversed\u2014for example, by preventing the action of the histone deacetylase protein that removes acetyl groups, or by DNA methyl transferase enzymes that add methyl groups to cytosines in DNA\u2014it is possible to design new drugs and new therapies to take advantage of the reversible nature of these processes. Indeed, many researchers are testing how a silenced gene can be switched back on in a cancer cell to help re-establish normal growth patterns.<\/p><p><span id=\"m44548-fs-id1958502\"> <\/span>Genes involved in the development of many other illnesses, ranging from allergies to inflammation to autism, are thought to be regulated by epigenetic mechanisms. As our knowledge of how genes are controlled deepens, new ways to treat diseases like cancer will emerge.<\/p><\/div><div class=\"section\" title=\"Cancer and Transcriptional Control\"><div class=\"titlepage\"><div><div><h3 id=\"m44548-fs-id1977751\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Transcriptional Control<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44548-fs-id2688570\"> <\/span>Alterations in cells that give rise to cancer can affect the transcriptional control of gene expression. Mutations that activate transcription factors, such as increased phosphorylation, can increase the binding of a transcription factor to its binding site in a promoter. This could lead to increased transcriptional activation of that gene that results in modified cell growth. Alternatively, a mutation in the DNA of a promoter or enhancer region can increase the binding ability of a transcription factor. This could also lead to the increased transcription and aberrant gene expression that is seen in cancer cells.<\/p><p><span id=\"m44548-fs-id2971281\"> <\/span>Researchers have been investigating how to control the transcriptional activation of gene expression in cancer. Identifying how a transcription factor binds, or a pathway that activates where a gene can be turned off, has led to new drugs and new ways to treat cancer. In breast cancer, for example, many proteins are overexpressed. This can lead to increased phosphorylation of key transcription factors that increase transcription. One such example is the overexpression of the epidermal growth factor receptor (EGFR) in a subset of breast cancers. The EGFR pathway activates many protein kinases that, in turn, activate many transcription factors that control genes involved in cell growth. New drugs that prevent the activation of EGFR have been developed and are used to treat these cancers.<\/p><\/div><div class=\"section\" title=\"Cancer and Post-transcriptional Control\"><div class=\"titlepage\"><div><div><h3 id=\"m44548-fs-id2749879\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Post-transcriptional Control<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44548-fs-id2595766\"> <\/span>Changes in the post-transcriptional control of a gene can also result in cancer. Recently, several groups of researchers have shown that specific cancers have altered expression of miRNAs. Because miRNAs bind to the 3' UTR of RNA molecules to degrade them, overexpression of these miRNAs could be detrimental to normal cellular activity. Too many miRNAs could dramatically decrease the RNA population leading to a decrease in protein expression. Several studies have demonstrated a change in the miRNA population in specific cancer types. It appears that the subset of miRNAs expressed in breast cancer cells is quite different from the subset expressed in lung cancer cells or even from normal breast cells. This suggests that alterations in miRNA activity can contribute to the growth of breast cancer cells. These types of studies also suggest that if some miRNAs are specifically expressed only in cancer cells, they could be potential drug targets. It would, therefore, be conceivable that new drugs that turn off miRNA expression in cancer could be an effective method to treat cancer.<\/p><\/div><div class=\"section\" title=\"Cancer and Translational\/Post-translational Control\"><div class=\"titlepage\"><div><div><h3 id=\"m44548-fs-id1988417\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Translational\/Post-translational Control<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44548-fs-id1953887\"> <\/span>There are many examples of how translational or post-translational modifications of proteins arise in cancer. Modifications are found in cancer cells from the increased translation of a protein to changes in protein phosphorylation to alternative splice variants of a protein. An example of how the expression of an alternative form of a protein can have dramatically different outcomes is seen in colon cancer cells. The c-Flip protein, a protein involved in mediating the cell death pathway, comes in two forms: long (c-FLIPL) and short (c-FLIPS). Both forms appear to be involved in initiating controlled cell death mechanisms in normal cells. However, in colon cancer cells, expression of the long form results in increased cell growth instead of cell death. Clearly, the expression of the wrong protein dramatically alters cell function and contributes to the development of cancer.<\/p><\/div><div class=\"section\" title=\"New Drugs to Combat Cancer: Targeted Therapies\"><div class=\"titlepage\"><div><div><h3 id=\"m44548-fs-idp254559760\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">New Drugs to Combat Cancer: Targeted Therapies<\/span><\/span><\/h3><\/div><\/div><\/div><p><span id=\"m44548-fs-id1812931\"> <\/span>Scientists are using what is known about the regulation of gene expression in disease states, including cancer, to develop new ways to treat and prevent disease development. Many scientists are designing drugs on the basis of the gene expression patterns within individual tumors. This idea, that therapy and medicines can be tailored to an individual, has given rise to the field of personalized medicine. With an increased understanding of gene regulation and gene function, medicines can be designed to specifically target diseased cells without harming healthy cells. Some new medicines, called targeted therapies, have exploited the overexpression of a specific protein or the mutation of a gene to develop a new medication to treat disease. One such example is the use of anti-EGF receptor medications to treat the subset of breast cancer tumors that have very high levels of the EGF protein. Undoubtedly, more targeted therapies will be developed as scientists learn more about how gene expression changes can cause cancer.<\/p><div id=\"m44548-fs-id2681687\" class=\"note career\"><div class=\"title\"><span class=\"cnx-gentext-tip-t\">Career Connection<\/span><\/div><div class=\"body\"><p title=\"Clinical Trial Coordinator\"><span id=\"m44548-fs-id1876201\"> <\/span><\/p><div class=\"title\"><b>Clinical Trial Coordinator<\/b><\/div><p title=\"Clinical Trial Coordinator\">A clinical trial coordinator is the person managing the proceedings of the clinical trial. This job includes coordinating patient schedules and appointments, maintaining detailed notes, building the database to track patients (especially for long-term follow-up studies), ensuring proper documentation has been acquired and accepted, and working with the nurses and doctors to facilitate the trial and publication of the results. A clinical trial coordinator may have a science background, like a nursing degree, or other certification. People who have worked in science labs or in clinical offices are also qualified to become a clinical trial coordinator. These jobs are generally in hospitals; however, some clinics and doctor\u2019s offices also conduct clinical trials and may hire a coordinator.<\/p><\/div><\/div><\/div><\/div><div class=\"glossary\" title=\"Glossary\" id=\"id521800\"><div class=\"titlepage\"><div><div><h2 class=\"title\"><span class=\"cnx-gentext-glossary cnx-gentext-autogenerated\"><span class=\"cnx-gentext-glossary cnx-gentext-t\">Glossary<\/span><\/span><\/h2><\/div><\/div><\/div><dl><dt><span class=\"emphasis\"><em>cis<\/em><\/span>-acting element<\/dt><dd><p>transcription factor binding sites within the promoter that regulate the transcription of a gene adjacent to it<\/p><\/dd><dt><span class=\"emphasis\"><em>trans<\/em><\/span>-acting element<\/dt><dd><p>transcription factor binding site found outside the promoter or on another chromosome that influences the transcription of a particular gene<\/p><\/dd><dt>3' UTR<\/dt><dd><p>3' untranslated region; region just downstream of the protein-coding region in an RNA molecule that is not translated<\/p><\/dd><dt>5' UTR<\/dt><dd><p>5' untranslated region; region just upstream of the protein-coding region in an RNA molecule that is not translated<\/p><\/dd><dt>5' cap<\/dt><dd><p>a methylated guanosine triphosphate (GTP) molecule that is attached to the 5' end of a messenger RNA to protect the end from degradation<\/p><\/dd><dt>activator<\/dt><dd><p>protein that binds to prokaryotic operators to increase transcription<\/p><\/dd><dt>catabolite activator protein (CAP)<\/dt><dd><p>protein that complexes with cAMP to bind to the promoter sequences of operons that control sugar processing when glucose is not available<\/p><\/dd><dt>DNA methylation<\/dt><dd><p>epigenetic modification that leads to gene silencing; commonly found in cancer cells<\/p><\/dd><dt>dicer<\/dt><dd><p>enzyme that chops the pre-miRNA into the mature form of the miRNA<\/p><\/dd><dt>enhancer<\/dt><dd><p>segment of DNA that is upstream, downstream, perhaps thousands of nucleotides away, or on another chromosome that influence the transcription of a specific gene<\/p><\/dd><dt>epigenetic<\/dt><dd><p>heritable changes that do not involve changes in the DNA sequence<\/p><\/dd><dt>eukaryotic initiation factor-2 (eIF-2)<\/dt><dd><p>protein that binds first to an mRNA to initiate translation<\/p><\/dd><dt>gene expression<\/dt><dd><p>processes that control the turning on or turning off of a gene<\/p><\/dd><dt>guanine diphosphate (GDP)<\/dt><dd><p> molecule that is left after the energy is used to start translation<\/p><\/dd><dt>guanine triphosphate (GTP)<\/dt><dd><p>energy-providing molecule that binds to eIF-2 and is needed for translation<\/p><\/dd><dt>histone acetylation<\/dt><dd><p>epigenetic modification that leads to gene silencing; commonly found in cancer cells found in cancer cells<\/p><\/dd><dt>inducible operon<\/dt><dd><p>operon that can be activated or repressed depending on cellular needs and the surrounding environment<\/p><\/dd><dt>initiation complex<\/dt><dd><p>protein complex containing eIF2-2 that starts translation<\/p><\/dd><dt>lac operon<\/dt><dd><p>operon in prokaryotic cells that encodes genes required for processing and intake of lactose<\/p><\/dd><dt>large 60S ribosomal subunit<\/dt><dd><p>second, larger ribosomal subunit that binds to the RNA to translate it into protein<\/p><\/dd><dt>microRNA (miRNA)<\/dt><dd><p>small RNA molecules (approximately 21 nucleotides in length) that bind to RNA molecules to degrade them<\/p><\/dd><dt>myc<\/dt><dd><p>oncogene that causes cancer in many cancer cells<\/p><\/dd><dt>negative regulator<\/dt><dd><p>protein that prevents transcription<\/p><\/dd><dt>operator<\/dt><dd><p>region of DNA outside of the promoter region that binds activators or repressors that control gene expression in prokaryotic cells<\/p><\/dd><dt>operon<\/dt><dd><p>collection of genes involved in a pathway that are transcribed together as a single mRNA in prokaryotic cells<\/p><\/dd><dt>poly-A tail<\/dt><dd><p>a series of adenine nucleotides that are attached to the 3' end of an mRNA to protect the end from degradation<\/p><\/dd><dt>positive regulator<\/dt><dd><p>protein that increases transcription<\/p><\/dd><dt>post-transcriptional<\/dt><dd><p>control of gene expression after the RNA molecule has been created but before it is translated into protein<\/p><\/dd><dt>post-translational<\/dt><dd><p>control of gene expression after a protein has been created<\/p><\/dd><dt>proteasome<\/dt><dd><p>organelle that degrades proteins<\/p><\/dd><dt>RISC<\/dt><dd><p>protein complex that binds along with the miRNA to the RNA to degrade it<\/p><\/dd><dt>RNA stability<\/dt><dd><p>how long an RNA molecule will remain intact in the cytoplasm<\/p><\/dd><dt>RNA-binding protein (RBP)<\/dt><dd><p>protein that binds to the 3' or 5' UTR to increase or decrease the RNA stability<\/p><\/dd><dt>repressor<\/dt><dd><p>protein that binds to the operator of prokaryotic genes to prevent transcription<\/p><\/dd><dt>small 40S ribosomal subunit<\/dt><dd><p>ribosomal subunit that binds to the RNA to translate it into protein<\/p><\/dd><dt>transcription factor binding site<\/dt><dd><p>sequence of DNA to which a transcription factor binds<\/p><\/dd><dt>transcription factor<\/dt><dd><p>protein that binds to the DNA at the promoter or enhancer region and that influences transcription of a gene<\/p><\/dd><dt>transcriptional start site<\/dt><dd><p>site at which transcription begins<\/p><\/dd><dt>trp operon<\/dt><dd><p>series of genes necessary to synthesize tryptophan in prokaryotic cells<\/p><\/dd><dt>tryptophan<\/dt><dd><p>amino acid that can be synthesized by prokaryotic cells when necessary<\/p><\/dd><dt>untranslated region<\/dt><dd><p>segment of the RNA molecule that are not translated into protein. These regions lie before (upstream or 5') and after (downstream or 3') the protein-coding region<\/p><\/dd><\/dl><\/div>&lt;!--CNX: Start Area: \"Sections Summary\"--&gt;<div class=\"cnx-eoc summary\"><div class=\"title\"><span>Sections Summary<\/span><\/div><div class=\"section empty\"><div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div><div class=\"body\"><div class=\"section\"><div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div><div class=\"body\"><p><span id=\"m44534-fs-id1899262\"> <\/span>While all somatic cells within an organism contain the same DNA, not all cells within that organism express the same proteins. Prokaryotic organisms express the entire DNA they encode in every cell, but not necessarily all at the same time. Proteins are expressed only when they are needed. Eukaryotic organisms express a subset of the DNA that is encoded in any given cell. In each cell type, the type and amount of protein is regulated by controlling gene expression. To express a protein, the DNA is first transcribed into RNA, which is then translated into proteins. In prokaryotic cells, these processes occur almost simultaneously. In eukaryotic cells, transcription occurs in the nucleus and is separate from the translation that occurs in the cytoplasm. Gene expression in prokaryotes is regulated only at the transcriptional level, whereas in eukaryotic cells, gene expression is regulated at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels.<\/p><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><p><span id=\"m44535-fs-idm214780208\"> <\/span>The regulation of gene expression in prokaryotic cells occurs at the transcriptional level. There are three ways to control the transcription of an operon: repressive control, activator control, and inducible control. Repressive control, typified by the<span class=\"emphasis\"><em> trp<\/em><\/span> operon, uses proteins bound to the operator sequence to physically prevent the binding of RNA polymerase and the activation of transcription. Therefore, if tryptophan is not needed, the repressor is bound to the operator and transcription remains off. Activator control, typified by the action of CAP, increases the binding ability of RNA polymerase to the promoter when CAP is bound. In this case, low levels of glucose result in the binding of cAMP to CAP. CAP then binds the promoter, which allows RNA polymerase to bind to the promoter better. In the last example\u2014the <span class=\"emphasis\"><em>lac<\/em><\/span> operon\u2014two conditions must be met to initiate transcription. Glucose must not be present, and lactose must be available for the <span class=\"emphasis\"><em>lac<\/em><\/span> operon to be transcribed. If glucose is absent, CAP binds to the operator. If lactose is present, the repressor protein does not bind to its operator. Only when both conditions are met will RNA polymerase bind to the promoter to induce transcription.<\/p><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><p><span id=\"m44536-fs-id2682880\"> <\/span>In eukaryotic cells, the first stage of gene expression control occurs at the epigenetic level. Epigenetic mechanisms control access to the chromosomal region to allow genes to be turned on or off. These mechanisms control how DNA is packed into the nucleus by regulating how tightly the DNA is wound around histone proteins. The addition or removal of chemical modifications (or flags) to histone proteins or DNA signals to the cell to open or close a chromosomal region. Therefore, eukaryotic cells can control whether a gene is expressed by controlling accessibility to transcription factors and the binding of RNA polymerase to initiate transcription.<\/p><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><p><span id=\"m44538-fs-id2155116\"> <\/span>To start transcription, general transcription factors, such as TFIID, TFIIH, and others, must first bind to the TATA box and recruit RNA polymerase to that location. The binding of additional regulatory transcription factors to <span class=\"emphasis\"><em>cis<\/em><\/span>-acting elements will either increase or prevent transcription. In addition to promoter sequences, enhancer regions help augment transcription. Enhancers can be upstream, downstream, within a gene itself, or on other chromosomes. Transcription factors bind to enhancer regions to increase or prevent transcription.<\/p><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><p><span id=\"m44539-fs-id2572217\"> <\/span>Post-transcriptional control can occur at any stage after transcription, including RNA splicing, nuclear shuttling, and RNA stability. Once RNA is transcribed, it must be processed to create a mature RNA that is ready to be translated. This involves the removal of introns that do not code for protein. Spliceosomes bind to the signals that mark the exon\/intron border to remove the introns and ligate the exons together. Once this occurs, the RNA is mature and can be translated. RNA is created and spliced in the nucleus, but needs to be transported to the cytoplasm to be translated. RNA is transported to the cytoplasm through the nuclear pore complex. Once the RNA is in the cytoplasm, the length of time it resides there before being degraded, called RNA stability, can also be altered to control the overall amount of protein that is synthesized. The RNA stability can be increased, leading to longer residency time in the cytoplasm, or decreased, leading to shortened time and less protein synthesis. RNA stability is controlled by RNA-binding proteins (RPBs) and microRNAs (miRNAs). These RPBs and miRNAs bind to the 5' UTR or the 3' UTR of the RNA to increase or decrease RNA stability. Depending on the RBP, the stability can be increased or decreased significantly; however, miRNAs always decrease stability and promote decay.<\/p><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><p><span id=\"m44542-fs-id1511868\"> <\/span>Changing the status of the RNA or the protein itself can affect the amount of protein, the function of the protein, or how long it is found in the cell. To translate the protein, a protein initiator complex must assemble on the RNA. Modifications (such as phosphorylation) of proteins in this complex can prevent proper translation from occurring. Once a protein has been synthesized, it can be modified (phosphorylated, acetylated, methylated, or ubiquitinated). These post-translational modifications can greatly impact the stability, degradation, or function of the protein.<\/p><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><p><span id=\"m44548-fs-id3321766\"> <\/span>Cancer can be described as a disease of altered gene expression. Changes at every level of eukaryotic gene expression can be detected in some form of cancer at some point in time. In order to understand how changes to gene expression can cause cancer, it is critical to understand how each stage of gene regulation works in normal cells. By understanding the mechanisms of control in normal, non-diseased cells, it will be easier for scientists to understand what goes wrong in disease states including complex ones like cancer.<\/p><\/div><\/div><\/div>&lt;!--CNX: Start Area: \"Art Connections\"--&gt;<div class=\"cnx-eoc art-exercise\"><div class=\"title\"><span>Art Connections<\/span><\/div><div class=\"section empty\"><div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div><div class=\"body\"><div class=\"section empty\"><div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div><div class=\"body\"><div class=\"section\"><div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44535-fs-idm113244368\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm111796848\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">5.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44535-fs-idm147603472\"> <\/span>    \n <p><span id=\"m44535-fs-idm144508512\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xA0;16.5.&#xA0;\">Figure\u00a016.5<\/a> In <span class=\"emphasis\"><em>E. coli<\/em><\/span>, the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is on by default, while the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is off. Why do you think that this is the case?<\/p>\n    <\/div><div id=\"m44535-fs-idm111796848\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm113244368\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44535-fs-idm18140960\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xA0;16.5.&#xA0;\">Figure\u00a016.5<\/a> Tryptophan is an amino acid essential for making proteins, so the cell always needs to have some on hand. However, if plenty of tryptophan is present, it is wasteful to make more, and the expression of the <span class=\"emphasis\"><em>trp<\/em><\/span> receptor is repressed. Lactose, a sugar found in milk, is not always available. It makes no sense to make the enzymes necessary to digest an energy source that is not available, so the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is only turned on when lactose is present.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44536-fs-id2134312\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id2596342\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">10.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44536-fs-id2138308\"> <\/span>    \n<p><span id=\"m44536-fs-id1260103\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xA0;16.7.&#xA0;\">Figure\u00a016.7<\/a> In females, one of the two X chromosomes is inactivated during embryonic development because of epigenetic changes to the chromatin. What impact do you think these changes would have on nucleosome packing?<\/p>\n<\/div><div id=\"m44536-fs-id2596342\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44536-fs-id2936478\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xA0;16.7.&#xA0;\">Figure\u00a016.7<\/a> The nucleosomes would pack more tightly together.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section empty\"><div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div class=\"section empty\"><div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div class=\"section\"><div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44542-fs-id2339974\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id1444395\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">22.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44542-fs-id2138282\"> <\/span>\n<p><span id=\"m44542-fs-id1974790\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xA0;16.13.&#xA0;\">Figure\u00a016.13<\/a> An increase in phosphorylation levels of eIF-2 has been observed in patients with neurodegenerative diseases such as Alzheimer\u2019s, Parkinson\u2019s, and Huntington\u2019s. What impact do you think this might have on protein synthesis?<\/p>\n<\/div><div id=\"m44542-fs-id1444395\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id2339974\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44542-fs-id2137736\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xA0;16.13.&#xA0;\">Figure\u00a016.13<\/a> Protein synthesis would be inhibited.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section empty\"><div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"\/>&lt;!--CNX: Start Area: \"Multiple Choice\"--&gt;<div class=\"cnx-eoc multiple-choice\"><div class=\"title\"><span>Multiple Choice<\/span><\/div><div class=\"section empty\"><div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div><div class=\"body\"><div class=\"section\"><div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44534-fs-id2187777\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id2745786\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">1.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44534-fs-id2689302\"> <\/span><p><span id=\"m44534-fs-id2162541\"> <\/span>Control of gene expression in eukaryotic cells occurs at which level(s)?<\/p>\n<div class=\"orderedlist\"><span id=\"m44534-fs-id1731340\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>only the transcriptional level<\/p><\/li><li class=\"listitem\"><p>epigenetic and transcriptional levels<\/p><\/li><li class=\"listitem\"><p>epigenetic, transcriptional, and translational levels<\/p><\/li><li class=\"listitem\"><p>epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44534-fs-id2745786\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2187777\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44534-fs-id2726499\"> <\/span>D<\/p><\/div><\/div><\/div><\/div><div id=\"m44534-fs-id1472236\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id2956599\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">2.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44534-fs-id1912048\"> <\/span><p><span id=\"m44534-fs-id3456527\"> <\/span>Post-translational control refers to:<\/p>\n<div class=\"orderedlist\"><span id=\"m44534-fs-id3274389\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>regulation of gene expression after transcription<\/p><\/li><li class=\"listitem\"><p>regulation of gene expression after translation<\/p><\/li><li class=\"listitem\"><p>control of epigenetic activation<\/p><\/li><li class=\"listitem\"><p>period between transcription and translation<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44534-fs-id2956599\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1472236\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44534-fs-id1511015\"> <\/span>B<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44535-fs-idm153813744\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm213368672\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">6.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44535-fs-idm88665920\"> <\/span><p><span id=\"m44535-fs-idm164517008\"> <\/span>If glucose is absent, but so is lactose, the <span class=\"emphasis\"><em>lac<\/em><\/span> operon will be ________.<\/p>\n<div class=\"orderedlist\"><span id=\"m44535-fs-idm120554128\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>activated<\/p><\/li><li class=\"listitem\"><p>repressed<\/p><\/li><li class=\"listitem\"><p>activated, but only partially<\/p><\/li><li class=\"listitem\"><p>mutated<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44535-fs-idm213368672\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm153813744\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44535-fs-idm70446512\"> <\/span>B<\/p><\/div><\/div><\/div><\/div><div id=\"m44535-fs-idm98160192\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm101679744\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">7.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44535-fs-idm75160576\"> <\/span><p><span id=\"m44535-fs-idm203465040\"> <\/span>Prokaryotic cells lack a nucleus. Therefore, the genes in prokaryotic cells are:<\/p>\n<div class=\"orderedlist\"><span id=\"m44535-fs-idm150743696\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>all expressed, all of the time<\/p><\/li><li class=\"listitem\"><p>transcribed and translated almost simultaneously<\/p><\/li><li class=\"listitem\"><p>transcriptionally controlled because translation begins before transcription ends<\/p><\/li><li class=\"listitem\"><p>b and c are both true<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44535-fs-idm101679744\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm98160192\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44535-fs-idm226775584\"> <\/span>D<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44536-fs-id3112360\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id1426316\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">11.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44536-fs-id1426330\"> <\/span><p><span id=\"m44536-fs-id2075390\"> <\/span>What are epigenetic modifications?<\/p>\n<div class=\"orderedlist\"><span id=\"m44536-fs-id2745125\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>the addition of reversible changes to histone proteins and DNA<\/p><\/li><li class=\"listitem\"><p>the removal of nucleosomes from the DNA<\/p><\/li><li class=\"listitem\"><p>the addition of more nucleosomes to the DNA<\/p><\/li><li class=\"listitem\"><p>mutation of the DNA sequence<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44536-fs-id1426316\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id3112360\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44536-fs-id1595223\"> <\/span>A<\/p><\/div><\/div><\/div><\/div><div id=\"m44536-fs-id2072168\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id2188544\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">12.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44536-fs-id1712063\"> <\/span><p><span id=\"m44536-fs-id1912048\"> <\/span>Which of the following are true of epigenetic changes?<\/p>\n<div class=\"orderedlist\"><span id=\"m44536-fs-id1723647\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>allow DNA to be transcribed<\/p><\/li><li class=\"listitem\"><p>move histones to open or close a chromosomal region<\/p><\/li><li class=\"listitem\"><p>are temporary<\/p><\/li><li class=\"listitem\"><p>all of the above<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44536-fs-id2188544\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2072168\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44536-fs-id1843643\"> <\/span>D<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44538-fs-id1808039\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id1962149\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">14.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44538-fs-id1723647\"> <\/span><p><span id=\"m44538-fs-id1260103\"> <\/span>The binding of ________ is required for transcription to start.<\/p>\n<div class=\"orderedlist\"><span id=\"m44538-fs-id1912269\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>a protein<\/p><\/li><li class=\"listitem\"><p>DNA polymerase<\/p><\/li><li class=\"listitem\"><p>RNA polymerase<\/p><\/li><li class=\"listitem\"><p>a transcription factor<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44538-fs-id1962149\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1808039\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44538-fs-id1627110\"> <\/span>C<\/p><\/div><\/div><\/div><\/div><div id=\"m44538-fs-id1394736\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id2595874\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">15.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44538-fs-id1309467\"> <\/span><p><span id=\"m44538-fs-id1594018\"> <\/span>What will result from the binding of a transcription factor to an enhancer region?<\/p>\n<div class=\"orderedlist\"><span id=\"m44538-fs-id2196025\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>decreased transcription of an adjacent gene<\/p><\/li><li class=\"listitem\"><p>increased transcription of a distant gene<\/p><\/li><li class=\"listitem\"><p>alteration of the translation of an adjacent gene<\/p><\/li><li class=\"listitem\"><p>initiation of the recruitment of RNA polymerase<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44538-fs-id2595874\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1394736\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44538-fs-id2385867\"> <\/span>B<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44539-fs-id2685625\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id1684950\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">18.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44539-fs-id1876100\"> <\/span><p><span id=\"m44539-fs-id1968588\"> <\/span>Which of the following are involved in post-transcriptional control?<\/p>\n<div class=\"orderedlist\"><span id=\"m44539-fs-id2642499\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>control of RNA splicing<\/p><\/li><li class=\"listitem\"><p>control of RNA shuttling<\/p><\/li><li class=\"listitem\"><p>control of RNA stability<\/p><\/li><li class=\"listitem\"><p>all of the above<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44539-fs-id1684950\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2685625\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44539-fs-id2585833\"> <\/span>D<\/p><\/div><\/div><\/div><\/div><div id=\"m44539-fs-id685962\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id2338011\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">19.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44539-fs-id2216370\"> <\/span><p><span id=\"m44539-fs-id2914078\"> <\/span>Binding of an RNA binding protein will ________ the stability of the RNA molecule.<\/p><div class=\"orderedlist\"><span id=\"m44539-fs-id1793945\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>increase<\/p><\/li><li class=\"listitem\"><p>decrease<\/p><\/li><li class=\"listitem\"><p>neither increase nor decrease<\/p><\/li><li class=\"listitem\"><p>either increase or decrease<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44539-fs-id2338011\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id685962\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44539-fs-id1426330\"> <\/span>D<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44542-fs-id1404412\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id1670772\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">23.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44542-fs-id1651216\"> <\/span><p><span id=\"m44542-fs-id1957056\"> <\/span>Post-translational modifications of proteins can affect which of the following?<\/p>\n<div class=\"orderedlist\"><span id=\"m44542-fs-id1442980\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>protein function<\/p><\/li><li class=\"listitem\"><p>transcriptional regulation<\/p><\/li><li class=\"listitem\"><p>chromatin modification<\/p><\/li><li class=\"listitem\"><p>all of the above<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44542-fs-id1670772\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1404412\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44542-fs-id2682995\"> <\/span>A<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44548-fs-id1674486\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id1361234\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">27.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44548-fs-id1424266\"> <\/span><p><span id=\"m44548-fs-id1964461\"> <\/span>Cancer causing genes are called ________.<\/p>\n<div class=\"orderedlist\"><span id=\"m44548-fs-id1719205\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>transformation genes<\/p><\/li><li class=\"listitem\"><p>tumor suppressor genes<\/p><\/li><li class=\"listitem\"><p>oncogenes<\/p><\/li><li class=\"listitem\"><p>mutated genes<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44548-fs-id1361234\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id1674486\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44548-fs-id1457647\"> <\/span>C<\/p><\/div><\/div><\/div><\/div><div id=\"m44548-fs-id2626129\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id2570415\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">28.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44548-fs-id2022725\"> <\/span><p><span id=\"m44548-fs-id2348084\"> <\/span>Targeted therapies are used in patients with a set gene expression pattern. A targeted therapy that prevents the activation of the estrogen receptor in breast cancer would be beneficial to which type of patient?<\/p>\n<div class=\"orderedlist\"><span id=\"m44548-fs-id2385448\"> <\/span><ol class=\"orderedlist\" type=\"a\"><li class=\"listitem\"><p>patients who express the EGFR receptor in normal cells<\/p><\/li><li class=\"listitem\"><p>patients with a mutation that inactivates the estrogen receptor<\/p><\/li><li class=\"listitem\"><p>patients with lots of the estrogen receptor expressed in their tumor<\/p><\/li><li class=\"listitem\"><p>patients that have no estrogen receptor expressed in their tumor<\/p><\/li><\/ol><\/div>\n<\/div><div id=\"m44548-fs-id2570415\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2626129\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44548-fs-id2169285\"> <\/span>C<\/p><\/div><\/div><\/div><\/div><\/div><\/div><\/div>&lt;!--CNX: Start Area: \"Free Response\"--&gt;<div class=\"cnx-eoc free-response\"><div class=\"title\"><span>Free Response<\/span><\/div><div class=\"section empty\"><div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div><div class=\"body\"><div class=\"section\"><div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44534-fs-id2475955\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id1569019\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">3.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44534-fs-id2918717\"> <\/span>\n<p><span id=\"m44534-fs-id1310287\"> <\/span>Name two differences between prokaryotic and eukaryotic cells and how these differences benefit multicellular organisms.<\/p>\n<\/div><div id=\"m44534-fs-id1569019\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2475955\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44534-fs-id1485528\"> <\/span>Eukaryotic cells have a nucleus, whereas prokaryotic cells do not. In eukaryotic cells, DNA is confined within the nuclear region. Because of this, transcription and translation are physically separated. This creates a more complex mechanism for the control of gene expression that benefits multicellular organisms because it compartmentalizes gene regulation.<\/p><p><span id=\"m44534-eip-idp46390576\"> <\/span>Gene expression occurs at many stages in eukaryotic cells, whereas in prokaryotic cells, control of gene expression only occurs at the transcriptional level. This allows for greater control of gene expression in eukaryotes and more complex systems to be developed. Because of this, different cell types can arise in an individual organism.<\/p><\/div><\/div><\/div><\/div><div id=\"m44534-fs-id1443560\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id2126300\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">4.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44534-fs-id1442893\"> <\/span><p><span id=\"m44534-fs-id2310144\"> <\/span>Describe how controlling gene expression will alter the overall protein levels in the cell.<\/p>\n<\/div><div id=\"m44534-fs-id2126300\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1443560\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44534-fs-id2914874\"> <\/span>The cell controls which proteins are expressed and to what level each protein is expressed in the cell. Prokaryotic cells alter the transcription rate to turn genes on or off. This method will increase or decrease protein levels in response to what is needed by the cell. Eukaryotic cells change the accessibility (epigenetic), transcription, or translation of a gene. This will alter the amount of RNA and the lifespan of the RNA to alter the amount of protein that exists. Eukaryotic cells also control protein translation to increase or decrease the overall levels. Eukaryotic organisms are much more complex and can manipulate protein levels by changing many stages in the process.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44535-fs-idm269564080\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm101659264\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">8.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44535-fs-idm224823216\"> <\/span><p><span id=\"m44535-fs-idm152304928\"> <\/span>Describe how transcription in prokaryotic cells can be altered by external stimulation such as excess lactose in the environment.<\/p><\/div><div id=\"m44535-fs-idm101659264\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm269564080\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44535-fs-idm106482176\"> <\/span>Environmental stimuli can increase or induce transcription in prokaryotic cells. In this example, lactose in the environment will induce the transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon, but only if glucose is not available in the environment.<\/p><\/div><\/div><\/div><\/div><div id=\"m44535-fs-idm20214992\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm214699984\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">9.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44535-fs-idm103662208\"> <\/span><p><span id=\"m44535-fs-idm159081360\"> <\/span>What is the difference between a repressible and an inducible operon?<\/p><\/div><div id=\"m44535-fs-idm214699984\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm20214992\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44535-fs-idm202138176\"> <\/span>A repressible operon uses a protein bound to the promoter region of a gene to keep the gene repressed or silent. This repressor must be actively removed in order to transcribe the gene. An inducible operon is either activated or repressed depending on the needs of the cell and what is available in the local environment.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44536-fs-id1876408\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id2025774\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">13.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44536-fs-id1318470\"> <\/span><p><span id=\"m44536-fs-id2009095\"> <\/span>In cancer cells, alteration to epigenetic modifications turns off genes that are normally expressed. Hypothetically, how could you reverse this process to turn these genes back on?<\/p><\/div><div id=\"m44536-fs-id2025774\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id1876408\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44536-fs-id2051513\"> <\/span>You can create medications that reverse the epigenetic processes (to add histone acetylation marks or to remove DNA methylation) and create an open chromosomal configuration.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44538-fs-id1942060\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id2317344\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">16.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44538-fs-id2573671\"> <\/span><p><span id=\"m44538-fs-id2570388\"> <\/span>A mutation within the promoter region can alter transcription of a gene. Describe how this can happen.<\/p><\/div><div id=\"m44538-fs-id2317344\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1942060\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44538-fs-id2269310\"> <\/span>A mutation in the promoter region can change the binding site for a transcription factor that normally binds to increase transcription. The mutation could either decrease the ability of the transcription factor to bind, thereby decreasing transcription, or it can increase the ability of the transcription factor to bind, thus increasing transcription.<\/p><\/div><\/div><\/div><\/div><div id=\"m44538-fs-id2025518\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id2169012\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">17.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44538-fs-id2574201\"> <\/span><p><span id=\"m44538-fs-id2272706\"> <\/span>What could happen if a cell had too much of an activating transcription factor present?<\/p><\/div><div id=\"m44538-fs-id2169012\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id2025518\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44538-fs-id2239602\"> <\/span>If too much of an activating transcription factor were present, then transcription would be increased in the cell. This could lead to dramatic alterations in cell function.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44539-fs-id1511123\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id2714180\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">20.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44539-fs-id2315152\"> <\/span><p><span id=\"m44539-fs-id2118982\"> <\/span>Describe how RBPs can prevent miRNAs from degrading an RNA molecule.<\/p><\/div><div id=\"m44539-fs-id2714180\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id1511123\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44539-fs-id3327891\"> <\/span>RNA binding proteins (RBP) bind to the RNA and can either increase or decrease the stability of the RNA. If they increase the stability of the RNA molecule, the RNA will remain intact in the cell for a longer period of time than normal. Since both RBPs and miRNAs bind to the RNA molecule, RBP can potentially bind first to the RNA and prevent the binding of the miRNA that will degrade it.<\/p><\/div><\/div><\/div><\/div><div id=\"m44539-fs-id2134312\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id1876054\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">21.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44539-fs-id2984456\"> <\/span><p><span id=\"m44539-fs-id1808039\"> <\/span>How can external stimuli alter post-transcriptional control of gene expression?<\/p><\/div><div id=\"m44539-fs-id1876054\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44539-fs-id1894654\"> <\/span>External stimuli can modify RNA-binding proteins (i.e., through phosphorylation of proteins) to alter their activity.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44542-fs-id1650941\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id2733341\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">24.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44542-fs-id1867175\"> <\/span><p><span id=\"m44542-fs-id3327918\"> <\/span>Protein modification can alter gene expression in many ways. Describe how phosphorylation of proteins can alter gene expression.<\/p><\/div><div id=\"m44542-fs-id2733341\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1650941\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44542-fs-id2638006\"> <\/span>Because proteins are involved in every stage of gene regulation, phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering the transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).<\/p><\/div><\/div><\/div><\/div><div id=\"m44542-fs-id1680861\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id2098858\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">25.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44542-fs-id2911418\"> <\/span><p><span id=\"m44542-fs-id2062329\"> <\/span>Alternative forms of a protein can be beneficial or harmful to a cell. What do you think would happen if too much of an alternative protein bound to the 3' UTR of an RNA and caused it to degrade?<\/p><\/div><div id=\"m44542-fs-id2098858\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1680861\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44542-fs-id2874182\"> <\/span>If the RNA degraded, then less of the protein that the RNA encodes would be translated. This could have dramatic implications for the cell.<\/p><\/div><\/div><\/div><\/div><div id=\"m44542-fs-id1259369\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id1364111\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">26.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44542-fs-id1771623\"> <\/span><p><span id=\"m44542-fs-id1511201\"> <\/span>Changes in epigenetic modifications alter the accessibility and transcription of DNA. Describe how environmental stimuli, such as ultraviolet light exposure, could modify gene expression.<\/p><\/div><div id=\"m44542-fs-id1364111\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1259369\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44542-fs-id1353371\"> <\/span>Environmental stimuli, like ultraviolet light exposure, can alter the modifications to the histone proteins or DNA. Such stimuli may change an actively transcribed gene into a silenced gene by removing acetyl groups from histone proteins or by adding methyl groups to DNA.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"section\"><div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div><div class=\"body\"><div id=\"m44548-fs-id2020932\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id2080482\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">29.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44548-fs-id1354125\"> <\/span><p><span id=\"m44548-fs-id2167622\"> <\/span>New drugs are being developed that decrease DNA methylation and prevent the removal of acetyl groups from histone proteins. Explain how these drugs could affect gene expression to help kill tumor cells.<\/p><\/div><div id=\"m44548-fs-id2080482\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2020932\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44548-fs-id2689865\"> <\/span>These drugs will keep the histone proteins and the DNA methylation patterns in the open chromosomal configuration so that transcription is feasible. If a gene is silenced, these drugs could reverse the epigenetic configuration to re-express the gene.<\/p><\/div><\/div><\/div><\/div><div id=\"m44548-fs-id2048357\" class=\"exercise\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id2935760\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">30.<\/span><\/a><\/span><\/div><div class=\"body\">&lt;!--calling informal.object--&gt;<div class=\"problem\"><span id=\"m44548-fs-id2319451\"> <\/span><p><span id=\"m44548-fs-id2057320\"> <\/span>How can understanding the gene expression pattern in a cancer cell tell you something about that specific form of cancer?<\/p><\/div><div id=\"m44548-fs-id2935760\" class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2048357\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span id=\"m44548-fs-id2660635\"> <\/span>Understanding which genes are expressed in a cancer cell can help diagnose the specific form of cancer. It can also help identify treatment options for that patient. For example, if a breast cancer tumor expresses the EGFR in high numbers, it might respond to specific anti-EGFR therapy. If that receptor is not expressed, it would not respond to that therapy.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><\/div><div class=\"cnx-eoc cnx-solutions\"><div class=\"title\">Solutions<\/div>&lt;!--CNX: Start Area: \"Art Connections\"--&gt;<div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm113244368\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xA0;16.5.&#xA0;\">Figure\u00a016.5<\/a> Tryptophan is an amino acid essential for making proteins, so the cell always needs to have some on hand. However, if plenty of tryptophan is present, it is wasteful to make more, and the expression of the <span class=\"emphasis\"><em>trp<\/em><\/span> receptor is repressed. Lactose, a sugar found in milk, is not always available. It makes no sense to make the enzymes necessary to digest an energy source that is not available, so the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is only turned on when lactose is present.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xA0;16.7.&#xA0;\">Figure\u00a016.7<\/a> The nucleosomes would pack more tightly together.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id2339974\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xA0;16.13.&#xA0;\">Figure\u00a016.13<\/a> Protein synthesis would be inhibited.<\/p><\/div><\/div>&lt;!--CNX: Start Area: \"Multiple Choice\"--&gt;<div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2187777\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>D<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1472236\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>B<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm153813744\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>B<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm98160192\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>D<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id3112360\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>A<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2072168\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>D<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1808039\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>C<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1394736\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>B<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2685625\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>D<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id685962\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>D<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1404412\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>A<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id1674486\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>C<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2626129\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>C<\/p><\/div><\/div>&lt;!--CNX: Start Area: \"Free Response\"--&gt;<div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2475955\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>Eukaryotic cells have a nucleus, whereas prokaryotic cells do not. In eukaryotic cells, DNA is confined within the nuclear region. Because of this, transcription and translation are physically separated. This creates a more complex mechanism for the control of gene expression that benefits multicellular organisms because it compartmentalizes gene regulation.<\/p><p><span> <\/span>Gene expression occurs at many stages in eukaryotic cells, whereas in prokaryotic cells, control of gene expression only occurs at the transcriptional level. This allows for greater control of gene expression in eukaryotes and more complex systems to be developed. Because of this, different cell types can arise in an individual organism.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1443560\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>The cell controls which proteins are expressed and to what level each protein is expressed in the cell. Prokaryotic cells alter the transcription rate to turn genes on or off. This method will increase or decrease protein levels in response to what is needed by the cell. Eukaryotic cells change the accessibility (epigenetic), transcription, or translation of a gene. This will alter the amount of RNA and the lifespan of the RNA to alter the amount of protein that exists. Eukaryotic cells also control protein translation to increase or decrease the overall levels. Eukaryotic organisms are much more complex and can manipulate protein levels by changing many stages in the process.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm269564080\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>Environmental stimuli can increase or induce transcription in prokaryotic cells. In this example, lactose in the environment will induce the transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon, but only if glucose is not available in the environment.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm20214992\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>A repressible operon uses a protein bound to the promoter region of a gene to keep the gene repressed or silent. This repressor must be actively removed in order to transcribe the gene. An inducible operon is either activated or repressed depending on the needs of the cell and what is available in the local environment.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id1876408\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>You can create medications that reverse the epigenetic processes (to add histone acetylation marks or to remove DNA methylation) and create an open chromosomal configuration.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1942060\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>A mutation in the promoter region can change the binding site for a transcription factor that normally binds to increase transcription. The mutation could either decrease the ability of the transcription factor to bind, thereby decreasing transcription, or it can increase the ability of the transcription factor to bind, thus increasing transcription.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id2025518\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>If too much of an activating transcription factor were present, then transcription would be increased in the cell. This could lead to dramatic alterations in cell function.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id1511123\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>RNA binding proteins (RBP) bind to the RNA and can either increase or decrease the stability of the RNA. If they increase the stability of the RNA molecule, the RNA will remain intact in the cell for a longer period of time than normal. Since both RBPs and miRNAs bind to the RNA molecule, RBP can potentially bind first to the RNA and prevent the binding of the miRNA that will degrade it.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>External stimuli can modify RNA-binding proteins (i.e., through phosphorylation of proteins) to alter their activity.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1650941\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>Because proteins are involved in every stage of gene regulation, phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering the transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1680861\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>If the RNA degraded, then less of the protein that the RNA encodes would be translated. This could have dramatic implications for the cell.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1259369\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>Environmental stimuli, like ultraviolet light exposure, can alter the modifications to the histone proteins or DNA. Such stimuli may change an actively transcribed gene into a silenced gene by removing acetyl groups from histone proteins or by adding methyl groups to DNA.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2020932\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>These drugs will keep the histone proteins and the DNA methylation patterns in the open chromosomal configuration so that transcription is feasible. If a gene is silenced, these drugs could reverse the epigenetic configuration to re-express the gene.<\/p><\/div><\/div><div class=\"solution labeled\">&lt;!--calling formal.object--&gt;<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2048357\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div><div class=\"body\"><p><span> <\/span>Understanding which genes are expressed in a cancer cell can help diagnose the specific form of cancer. It can also help identify treatment options for that patient. For example, if a breast cancer tumor expresses the EGFR in high numbers, it might respond to specific anti-EGFR therapy. If that receptor is not expressed, it would not respond to that therapy.<\/p><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div>","rendered":"<div class=\"chapter\" title=\"Chapter&#xa0;16.&#xa0;Gene Expression\" id=\"id516614\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h1 class=\"title\"><span class=\"cnx-gentext-chapter cnx-gentext-autogenerated\">Chapter\u00a0<\/span><span class=\"cnx-gentext-chapter cnx-gentext-n\">16<\/span><span class=\"cnx-gentext-chapter cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-chapter cnx-gentext-t\">Gene Expression<\/span><\/h1>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"introduction\" id=\"m44533\">\n<div id=\"m44533-fig-ch16_00_01\" class=\"figure splash\" title=\"Figure&#xa0;16.1.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44533-fs-id1435492\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155830\/Figure_16_00_01.jpg\" width=\"700\" alt=\"Part A depicts a cross section of an eyeball, which has a lens at the front and a cluster of blood vessels at the back. Part B depicts a liver, which is shaped like a triangle. Beneath the liver is a lobe-shaped gall bladder connected to a pancreas by a stem-like vessel. Part C is a sketch, drawn by Leonardo Da Vinci, of a man standing erect with outstretched arms. Superimposed on this image, the man has his legs spread and his arms uplifted.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">The genetic content of each somatic cell in an organism is the same, but not all genes are expressed in every cell. The control of which genes are expressed dictates whether a cell is (a) an eye cell or (b) a liver cell. It is the differential gene expression patterns that arise in different cells that give rise to (c) a complete organism.<\/div>\n<\/div>\n<h3 class=\"title\"><span>Introduction<sup><a href=\"co03.html#book-attribution-m44533\">*<\/a><\/sup><\/span><\/h3>\n<p><span id=\"m44533-fs-id1595873\"> <\/span>Each somatic cell in the body generally contains the same DNA. A few exceptions include red blood cells, which contain no DNA in their mature state, and some immune system cells that rearrange their DNA while producing antibodies. In general, however, the genes that determine whether you have green eyes, brown hair, and how fast you metabolize food are the same in the cells in your eyes and your liver, even though these organs function quite differently. If each cell has the same DNA, how is it that cells or organs are different? Why do cells in the eye differ so dramatically from cells in the liver?<\/p>\n<p><span id=\"m44533-fs-id2059567\"> <\/span>Whereas each cell shares the same genome and DNA sequence, each cell does not turn on, or express, the same set of genes. Each cell type needs a different set of proteins to perform its function. Therefore, only a small subset of proteins is expressed in a cell. For the proteins to be expressed, the DNA must be transcribed into RNA and the RNA must be translated into protein. In a given cell type, not all genes encoded in the DNA are transcribed into RNA or translated into protein because specific cells in our body have specific functions. Specialized proteins that make up the eye (iris, lens, and cornea) are only expressed in the eye, whereas the specialized proteins in the heart (pacemaker cells, heart muscle, and valves) are only expressed in the heart. At any given time, only a subset of all of the genes encoded by our DNA are expressed and translated into proteins. The expression of specific genes is a highly regulated process with many levels and stages of control. This complexity ensures the proper expression in the proper cell at the proper time.<\/p>\n<\/div>\n<div xml:lang=\"en\" class=\"section module\" title=\"16.1.&#xa0;Regulation of Gene Expression\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<sup><a href=\"co03.html#book-attribution-m44534\">*<\/a><\/sup><\/span><\/span><\/h2>\n<\/div>\n<div class=\"abstract\">\n<div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"><\/span><\/span><\/span><\/div>\n<p>By the end of this section, you will be able to:\n<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">\n<p>Discuss why every cell does not express all of its genes<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Describe how prokaryotic gene regulation occurs at the transcriptional level<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Discuss how eukaryotic gene regulation occurs at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"toc\">\n<ul>\n<li class=\"toc-section\"><a href=\"#m44534-fs-id2300410\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic versus Eukaryotic Gene Expression<\/span><\/a><\/li>\n<\/ul>\n<\/div>\n<p><span id=\"m44534-fs-id1367090\"> <\/span>For a cell to function properly, necessary proteins must be synthesized at the proper time. All cells control or regulate the synthesis of proteins from information encoded in their DNA. The process of turning on a gene to produce RNA and protein is called <em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1684185\"> <\/span>gene expression<\/em><a id=\"id517191\" class=\"indexterm\">. Whether in a simple unicellular organism or a complex multi-cellular organism, each cell controls when and how its genes are expressed. For this to occur, there must be a mechanism to control when a gene is expressed to make RNA and protein, how much of the protein is made, and when it is time to stop making that protein because it is no longer needed.<\/a><\/p>\n<p><span id=\"m44534-fs-id2989558\"> <\/span>The regulation of gene expression conserves energy and space. It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required. In addition, only expressing a subset of genes in each cell saves space because DNA must be unwound from its tightly coiled structure to transcribe and translate the DNA. Cells would have to be enormous if every protein were expressed in every cell all the time.<\/p>\n<p><span id=\"m44534-fs-id2626522\"> <\/span>The control of gene expression is extremely complex. Malfunctions in this process are detrimental to the cell and can lead to the development of many diseases, including cancer.<\/p>\n<div class=\"section\" title=\"Prokaryotic versus Eukaryotic Gene Expression\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44534-fs-id2300410\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic versus Eukaryotic Gene Expression<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44534-fs-id2011802\"> <\/span>To understand how gene expression is regulated, we must first understand how a gene codes for a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different manners.<\/p>\n<p><span id=\"m44534-fs-id2988639\"> <\/span>Prokaryotic organisms are single-celled organisms that lack a cell nucleus, and their DNA therefore floats freely in the cell cytoplasm. To synthesize a protein, the processes of transcription and translation occur almost simultaneously. When the resulting protein is no longer needed, transcription stops. As a result, the primary method to control what type of protein and how much of each protein is expressed in a prokaryotic cell is the regulation of DNA transcription. All of the subsequent steps occur automatically. When more protein is required, more transcription occurs. Therefore, in prokaryotic cells, the control of gene expression is mostly at the transcriptional level.<\/p>\n<p><span id=\"m44534-fs-id1446467\"> <\/span>Eukaryotic cells, in contrast, have intracellular organelles that add to their complexity. In eukaryotic cells, the DNA is contained inside the cell\u2019s nucleus and there it is transcribed into RNA. The newly synthesized RNA is then transported out of the nucleus into the cytoplasm, where ribosomes translate the RNA into protein. The processes of transcription and translation are physically separated by the nuclear membrane; transcription occurs only within the nucleus, and translation occurs only outside the nucleus in the cytoplasm. The regulation of gene expression can occur at all stages of the process (<a class=\"xref target-figure\" href=\"ch16.html#m44534-fig-ch16_01_01\" title=\"Figure&#xa0;16.2.&#xa0;\">Figure\u00a016.2<\/a>). Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (<em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1688359\"> <\/span>epigenetic<\/em><a id=\"id517288\" class=\"indexterm\"> level), when the RNA is transcribed (transcriptional level), when the RNA is processed and exported to the cytoplasm after it is transcribed (<em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1688363\"> <\/span>post-transcriptional<\/em><\/a><a id=\"id517303\" class=\"indexterm\"> level), when the RNA is translated into protein (translational level), or after the protein has been made (<em class=\"glossterm\"><span id=\"m44534-autoid-cnx2dbk-id1688368\"> <\/span>post-translational<\/em><\/a><a id=\"id517317\" class=\"indexterm\"> level).<\/a><\/p>\n<div id=\"m44534-fig-ch16_01_01\" class=\"figure\" title=\"Figure&#xa0;16.2.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44534-fs-id1568395\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155833\/Figure_16_01_01.jpg\" width=\"550\" alt=\"Prokaryotic cells do not have a nucleus, and DNA is located in the cytoplasm. Ribosomes attach to the mRNA as it is being transcribed from DNA. Thus, transcription and translation occur simultaneously. In eukaryotic cells, the DNA is located in the nucleus, and ribosomes are located in the cytoplasm. After being transcribed, pre-mRNA is processed in the nucleus to make the mature mRNA, which is then exported to the cytoplasm where ribosomes become associated with it and translation begins.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">Prokaryotic transcription and translation occur simultaneously in the cytoplasm, and regulation occurs at the transcriptional level. Eukaryotic gene expression is regulated during transcription and RNA processing, which take place in the nucleus, and during protein translation, which takes place in the cytoplasm. Further regulation may occur through post-translational modifications of proteins.<\/div>\n<\/div>\n<p><span id=\"m44534-fs-id1444103\"> <\/span>The differences in the regulation of gene expression between prokaryotes and eukaryotes are summarized in <a class=\"xref target-table\" href=\"ch16.html#m44534-tab-ch16_01_01\" title=\"Table&#xa0;16.1.&#xa0;\">Table\u00a016.1<\/a>. The regulation of gene expression is discussed in detail in subsequent modules.<\/p>\n<div class=\"table\" id=\"m44534-tab-ch16_01_01\">\n<table cellpadding=\"0\" style=\"border: 1px solid; border-spacing: 0px;\">\n<caption><span class=\"cnx-gentext-caption cnx-gentext-t\">Table <\/span><span class=\"cnx-gentext-caption cnx-gentext-n\">16.1. <\/span><\/caption>\n<thead valign=\"bottom\">\n<tr>\n<th colspan=\"2\" style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">Differences in the Regulation of Gene Expression of Prokaryotic and Eukaryotic Organisms<\/th>\n<\/tr>\n<tr>\n<th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Prokaryotic organisms<\/th>\n<th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">Eukaryotic organisms<\/th>\n<\/tr>\n<\/thead>\n<tbody valign=\"top\">\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: left !important;\">Lack nucleus<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">Contain nucleus<\/td>\n<\/tr>\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: left !important;\">DNA is found in the cytoplasm<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">DNA is confined to the nuclear compartment<\/td>\n<\/tr>\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: left !important;\">RNA transcription and protein formation occur almost simultaneously<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">RNA transcription occurs prior to protein formation, and it takes place in the nucleus. Translation of RNA to protein occurs in the cytoplasm.<\/td>\n<\/tr>\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: left !important;\">Gene expression is regulated primarily at the transcriptional level<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 0 !important; text-align: left !important;\">Gene expression is regulated at many levels (epigenetic, transcriptional, nuclear shuttling, post-transcriptional, translational, and post-translational)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div id=\"m44534-fs-id2853732\" class=\"note evolution\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Evolution Connection<\/span><\/div>\n<div class=\"body\">\n<p title=\"Evolution of Gene Regulation\"><span id=\"m44534-fs-id2054814\"> <\/span><\/p>\n<div class=\"title\"><b>Evolution of Gene Regulation<\/b><\/div>\n<p title=\"Evolution of Gene Regulation\">Prokaryotic cells can only regulate gene expression by controlling the amount of transcription. As eukaryotic cells evolved, the complexity of the control of gene expression increased. For example, with the evolution of eukaryotic cells came compartmentalization of important cellular components and cellular processes. A nuclear region that contains the DNA was formed. Transcription and translation were physically separated into two different cellular compartments. It therefore became possible to control gene expression by regulating transcription in the nucleus, and also by controlling the RNA levels and protein translation present outside the nucleus.<\/p>\n<p><span id=\"m44534-fs-id1435492\"> <\/span>Some cellular processes arose from the need of the organism to defend itself. Cellular processes such as gene silencing developed to protect the cell from viral or parasitic infections. If the cell could quickly shut off gene expression for a short period of time, it would be able to survive an infection when other organisms could not. Therefore, the organism evolved a new process that helped it survive, and it was able to pass this new development to offspring.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div xml:lang=\"en\" class=\"section module\" title=\"16.2.&#xa0;Prokaryotic Gene Regulation\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<sup><a href=\"co03.html#book-attribution-m44535\">*<\/a><\/sup><\/span><\/span><\/h2>\n<\/div>\n<div class=\"abstract\">\n<div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"><\/span><\/span><\/span><\/div>\n<p>By the end of this section, you will be able to:\n<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">\n<p>Describe the steps involved in prokaryotic gene regulation<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Explain the roles of activators, inducers, and repressors in gene regulation<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"toc\">\n<ul>\n<li class=\"toc-section\"><a href=\"#m44535-fs-idm82649424\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>trp<\/em><\/span> Operon: A Repressor Operon<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44535-fs-idm202194608\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Catabolite Activator Protein (CAP): An Activator Regulator<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44535-fs-idm146228272\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>lac<\/em><\/span> Operon: An Inducer Operon<\/span><\/a><\/li>\n<\/ul>\n<\/div>\n<p><span id=\"m44535-fs-idm200418880\"> <\/span>The DNA of prokaryotes is organized into a circular chromosome supercoiled in the nucleoid region of the cell cytoplasm. Proteins that are needed for a specific function, or that are involved in the same biochemical pathway, are encoded together in blocks called <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1254793\"> <\/span>operons<\/em><a id=\"id517973\" class=\"indexterm\">. For example, all of the genes needed to use lactose as an energy source are coded next to each other in the lactose (or <span class=\"emphasis\"><em>lac<\/em><\/span>) operon.<\/a><\/p>\n<p><span id=\"m44535-fs-idm204458112\"> <\/span>In prokaryotic cells, there are three types of regulatory molecules that can affect the expression of operons: repressors, activators, and inducers. <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1254811\"> <\/span>Repressors<\/em><a id=\"id518002\" class=\"indexterm\"> are proteins that suppress transcription of a gene in response to an external stimulus, whereas <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1254815\"> <\/span>activators<\/em><\/a><a id=\"id518016\" class=\"indexterm\"> are proteins that increase the transcription of a gene in response to an external stimulus. Finally, inducers are small molecules that either activate or repress transcription depending on the needs of the cell and the availability of substrate.<\/a><\/p>\n<div class=\"section\" title=\"The trp Operon: A Repressor Operon\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44535-fs-idm82649424\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>trp<\/em><\/span> Operon: A Repressor Operon<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44535-fs-idm166815232\"> <\/span>Bacteria such as <span class=\"emphasis\"><em>E. coli<\/em><\/span> need amino acids to survive. <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1676419\"> <\/span>Tryptophan<\/em><a id=\"id518058\" class=\"indexterm\"> is one such amino acid that <span class=\"emphasis\"><em>E. coli<\/em><\/span> can ingest from the environment. <span class=\"emphasis\"><em>E. coli<\/em><\/span> can also synthesize tryptophan using enzymes that are encoded by five genes. These five genes are next to each other in what is called the <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1676435\"> <\/span>tryptophan (<span class=\"emphasis\"><em>trp<\/em><\/span>) operon<\/em><\/a><a id=\"id518091\" class=\"indexterm\"> (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_01\" title=\"Figure&#xa0;16.3.&#xa0;\">Figure\u00a016.3<\/a>). If tryptophan is present in the environment, then <span class=\"emphasis\"><em>E. coli<\/em><\/span> does not need to synthesize it and the switch controlling the activation of the genes in the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is switched off. However, when tryptophan availability is low, the switch controlling the operon is turned on, transcription is initiated, the genes are expressed, and tryptophan is synthesized.<\/p>\n<div id=\"m44535-fig-ch16_02_01\" class=\"figure\" title=\"Figure&#xa0;16.3.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44535-fs-idm229109280\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155835\/Figure_16_02_01.jpg\" width=\"450\" alt=\"The trp operon has a promoter, an operator, and five genes named trpE, trpD, trpC, trpB, and trpA that are located in sequential order on the DNA. RNA polymerase binds to the promoter. When tryptophan is present, the trp repressor binds the operator and prevents the RNA polymerase from moving past the operator; therefore, RNA synthesis is blocked. In the absence of tryptophan, the repressor dissociates from the operator. RNA polymerase can now slide past the operator, and transcription begins.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">The five genes that are needed to synthesize tryptophan in <span class=\"emphasis\"><em>E. coli<\/em><\/span> are located next to each other in the <span class=\"emphasis\"><em>trp<\/em><\/span> operon. When tryptophan is plentiful, two tryptophan molecules bind the repressor protein at the operator sequence. This physically blocks the RNA polymerase from transcribing the tryptophan genes. When tryptophan is absent, the repressor protein does not bind to the operator and the genes are transcribed.<\/div>\n<\/div>\n<p><span id=\"m44535-fs-idm174533984\"> <\/span>A DNA sequence that codes for proteins is referred to as the coding region. The five coding regions for the tryptophan biosynthesis enzymes are arranged sequentially on the chromosome in the operon. Just before the coding region is the <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1391232\"> <\/span>transcriptional start site<\/em><a id=\"id518195\" class=\"indexterm\">. This is the region of DNA to which RNA polymerase binds to initiate transcription. The promoter sequence is upstream of the transcriptional start site; each operon has a sequence within or near the promoter to which proteins (activators or repressors) can bind and regulate transcription.<\/a><\/p>\n<p><span id=\"m44535-fs-idm199850336\"> <\/span>A DNA sequence called the operator sequence is encoded between the promoter region and the first <span class=\"emphasis\"><em>trp<\/em><\/span> coding gene. This <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1391250\"> <\/span>operator<\/em><a id=\"id518225\" class=\"indexterm\"> contains the DNA code to which the repressor protein can bind. When tryptophan is present in the cell, two tryptophan molecules bind to the <span class=\"emphasis\"><em>trp<\/em><\/span> repressor, which changes shape to bind to the <span class=\"emphasis\"><em>trp<\/em><\/span> operator. Binding of the tryptophan\u2013repressor complex at the operator physically prevents the RNA polymerase from binding, and transcribing the downstream genes.<\/a><\/p>\n<p><span id=\"m44535-fs-idm101642592\"> <\/span>When tryptophan is not present in the cell, the repressor by itself does not bind to the operator; therefore, the operon is active and tryptophan is synthesized. Because the repressor protein actively binds to the operator to keep the genes turned off, the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is negatively regulated and the proteins that bind to the operator to silence <span class=\"emphasis\"><em>trp<\/em><\/span> expression are <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1619494\"> <\/span>negative regulators<\/em><a id=\"id518276\" class=\"indexterm\">.<\/a><\/p>\n<div id=\"m44535-fs-idm187290400\" class=\"note interactive\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div>\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44535-fs-idm20710464\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155837\/trp_operon.png\" width=\"130\" alt=\"QR Code representing a URL\" \/><\/div>\n<p><span id=\"m44535-fs-idm19622064\"> <\/span>Watch <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/trp_operon\" target=\"\">this video<\/a> to learn more about the <span class=\"emphasis\"><em>trp<\/em><\/span> operon.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\" title=\"Catabolite Activator Protein (CAP): An Activator Regulator\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44535-fs-idm202194608\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Catabolite Activator Protein (CAP): An Activator Regulator<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44535-fs-idm148740496\"> <\/span>Just as the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is negatively regulated by tryptophan molecules, there are proteins that bind to the operator sequences that act as a <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1634555\"> <\/span>positive regulator<\/em><a id=\"id518375\" class=\"indexterm\"> to turn genes on and activate them. For example, when glucose is scarce, <span class=\"emphasis\"><em>E. coli<\/em><\/span> bacteria can turn to other sugar sources for fuel. To do this, new genes to process these alternate genes must be transcribed. When glucose levels drop, cyclic AMP (cAMP) begins to accumulate in the cell. The cAMP molecule is a signaling molecule that is involved in glucose and energy metabolism in <span class=\"emphasis\"><em>E. coli<\/em><\/span>. When glucose levels decline in the cell, accumulating cAMP binds to the positive regulator <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1643183\"> <\/span>catabolite activator protein (CAP)<\/em><\/a><a id=\"id518404\" class=\"indexterm\">, a protein that binds to the promoters of operons that control the processing of alternative sugars. When cAMP binds to CAP, the complex binds to the promoter region of the genes that are needed to use the alternate sugar sources (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_02\" title=\"Figure&#xa0;16.4.&#xa0;\">Figure\u00a016.4<\/a>). In these operons, a CAP binding site is located upstream of the RNA polymerase binding site in the promoter. This increases the binding ability of RNA polymerase to the promoter region and the transcription of the genes.<\/p>\n<div id=\"m44535-fig-ch16_02_02\" class=\"figure\" title=\"Figure&#xa0;16.4.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44535-fs-idm287484176\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155839\/Figure_16_02_02.jpg\" width=\"450\" alt=\"The lac operon consists of a promoter, an operator, and three genes named lacZ, lacY, and lacA that are located in sequential order on the DNA. In the absence of cAMP, the CAP protein does not bind the DNA. RNA polymerase binds the promoter, and transcription occurs at a slow rate. In the presence of cAMP, a CAP&#x2013;cAMP complex binds to the promoter and increases RNA polymerase activity. As a result, the rate of RNA synthesis is increased.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">When glucose levels fall, <span class=\"emphasis\"><em>E. coli<\/em><\/span> may use other sugars for fuel but must transcribe new genes to do so. As glucose supplies become limited, cAMP levels increase. This cAMP binds to the CAP protein, a positive regulator that binds to an operator region upstream of the genes required to use other sugar sources.<\/div>\n<\/div>\n<\/div>\n<div class=\"section\" title=\"The lac Operon: An Inducer Operon\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44535-fs-idm146228272\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The <span class=\"emphasis\"><em>lac<\/em><\/span> Operon: An Inducer Operon<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44535-fs-idm17029296\"> <\/span>The third type of gene regulation in prokaryotic cells occurs through <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1276100\"> <\/span>inducible operons<\/em><a id=\"id518497\" class=\"indexterm\">, which have proteins that bind to activate or repress transcription depending on the local environment and the needs of the cell. The <span class=\"emphasis\"><em>lac<\/em><\/span> operon is a typical inducible operon. As mentioned previously, <span class=\"emphasis\"><em>E. coli<\/em><\/span> is able to use other sugars as energy sources when glucose concentrations are low. To do so, the cAMP\u2013CAP protein complex serves as a positive regulator to induce transcription. One such sugar source is lactose. The <em class=\"glossterm\"><span id=\"m44535-autoid-cnx2dbk-id1657851\"> <\/span><span class=\"emphasis\"><em>lac<\/em><\/span> operon<\/em><\/a><a id=\"id518534\" class=\"indexterm\"> encodes the genes necessary to acquire and process the lactose from the local environment. CAP binds to the operator sequence upstream of the promoter that initiates transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon. However, for the <span class=\"emphasis\"><em>lac<\/em><\/span> operon to be activated, two conditions must be met. First, the level of glucose must be very low or non-existent. Second, lactose must be present. Only when glucose is absent and lactose is present will the <span class=\"emphasis\"><em>lac<\/em><\/span> operon be transcribed (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xa0;16.5.&#xa0;\">Figure\u00a016.5<\/a>). This makes sense for the cell, because it would be energetically wasteful to create the proteins to process lactose if glucose was plentiful or lactose was not available.<\/p>\n<div id=\"m44535-fs-idm178239648\" class=\"note art-connection\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Art Connection<\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44535-fs-idm151012288\"> <\/span>\n<\/p>\n<div id=\"m44535-fig-ch16_02_03\" class=\"figure\" title=\"Figure&#xa0;16.5.&#xa0;\">\n<div class=\"body\"><span class=\"inlinemediaobject\"><span id=\"m44535-fs-idm178409184\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155841\/Figure_16_02_03.png\" width=\"300\" alt=\"The lac operon consists of a promoter, an operator, and three genes named lacZ, lacY, and lacA. RNA polymerase binds to the promoter. In the absence of lactose, the lac repressor binds to the operator and prevents RNA polymerase from transcribing the operon. In the presence of lactose, the repressor is released from the operator, and transcription proceeds at a slow rate. Binding of the cAMP&#x2013;CAP complex to the promoter stimulates RNA polymerase activity and increases RNA synthesis. However, even in the presence of the cAMP&#x2013;CAP complex, RNA synthesis is blocked if the repressor binds to the promoter.\" \/><\/span><\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">Transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is carefully regulated so that its expression only occurs when glucose is limited and lactose is present to serve as an alternative fuel source.<\/div>\n<\/div>\n<p><span id=\"m44535-fs-idm33204592\"> <\/span>In <span class=\"emphasis\"><em>E. coli<\/em><\/span>, the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is on by default, while the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is off. Why do you think this is the case?<\/p>\n<\/div>\n<\/div>\n<p><span id=\"m44535-fs-idm153663040\"> <\/span>If glucose is absent, then CAP can bind to the operator sequence to activate transcription. If lactose is absent, then the repressor binds to the operator to prevent transcription. If either of these requirements is met, then transcription remains off. Only when both conditions are satisfied is the <span class=\"emphasis\"><em>lac<\/em><\/span> operon transcribed (<a class=\"xref target-table\" href=\"ch16.html#m44535-tab-ch16_02_01\" title=\"Table&#xa0;16.2.&#xa0;\">Table\u00a016.2<\/a>).<\/p>\n<div class=\"table\" id=\"m44535-tab-ch16_02_01\">\n<table cellpadding=\"0\" style=\"border: 1px solid; border-spacing: 0px;\">\n<caption><span class=\"cnx-gentext-caption cnx-gentext-t\">Table <\/span><span class=\"cnx-gentext-caption cnx-gentext-n\">16.2. <\/span><\/caption>\n<thead valign=\"bottom\">\n<tr>\n<th colspan=\"5\" style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: left !important;\">Signals that Induce or Repress Transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> Operon<\/th>\n<\/tr>\n<tr>\n<th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Glucose<\/th>\n<th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">CAP binds<\/th>\n<th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Lactose<\/th>\n<th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">Repressor binds<\/th>\n<th style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">Transcription<\/th>\n<\/tr>\n<\/thead>\n<tbody valign=\"top\">\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">No<\/td>\n<\/tr>\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">Some<\/td>\n<\/tr>\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 1px solid; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 1px solid; text-align: center !important;\">No<\/td>\n<\/tr>\n<tr>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">+<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 1px solid; border-bottom: 0 !important; text-align: center !important;\">&#8211;<\/td>\n<td style=\"border-left: 0 !important; border-top: 0 !important; border-right: 0 !important; border-bottom: 0 !important; text-align: center !important;\">Yes<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div id=\"m44535-fs-idm116103472\" class=\"note interactive\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div>\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44535-fs-idp49045184\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155843\/lac_operon.png\" width=\"120\" alt=\"QR Code representing a URL\" \/><\/div>\n<p><span id=\"m44535-fs-idm187859568\"> <\/span>Watch an <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/lac_operon\" target=\"\">animated tutorial<\/a> about the workings of <span class=\"emphasis\"><em>lac<\/em><\/span> operon here.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div xml:lang=\"en\" class=\"section module\" title=\"16.3.&#xa0;Eukaryotic Epigenetic Gene Regulation\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<sup><a href=\"co03.html#book-attribution-m44536\">*<\/a><\/sup><\/span><\/span><\/h2>\n<\/div>\n<div class=\"abstract\">\n<div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"><\/span><\/span><\/span><\/div>\n<p>By the end of this section, you will be able to:\n<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">\n<p>Explain the process of epigenetic regulation<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Describe how access to DNA is controlled by histone modification<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"toc\">\n<ul>\n<li class=\"toc-section\"><a href=\"#m44536-fs-id1896201\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Epigenetic Control: Regulating Access to Genes within the Chromosome<\/span><\/a><\/li>\n<\/ul>\n<\/div>\n<p><span id=\"m44536-fs-id2990488\"> <\/span>Eukaryotic gene expression is more complex than prokaryotic gene expression because the processes of transcription and translation are physically separated. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at many different levels. Eukaryotic gene expression begins with control of access to the DNA. This form of regulation, called epigenetic regulation, occurs even before transcription is initiated.<\/p>\n<div class=\"section\" title=\"Epigenetic Control: Regulating Access to Genes within the Chromosome\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44536-fs-id1896201\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Epigenetic Control: Regulating Access to Genes within the Chromosome<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44536-fs-id1524776\"> <\/span>The human genome encodes over 20,000 genes; each of the 23 pairs of human chromosomes encodes thousands of genes. The DNA in the nucleus is precisely wound, folded, and compacted into chromosomes so that it will fit into the nucleus. It is also organized so that specific segments can be accessed as needed by a specific cell type.<\/p>\n<p><span id=\"m44536-fs-id2425348\"> <\/span>The first level of organization, or packing, is the winding of DNA strands around histone proteins. Histones package and order DNA into structural units called nucleosome complexes, which can control the access of proteins to the DNA regions (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_01\" title=\"Figure&#xa0;16.6.&#xa0;\">Figure\u00a016.6<\/a><span class=\"bold\"><strong>a<\/strong><\/span>). Under the electron microscope, this winding of DNA around histone proteins to form nucleosomes looks like small beads on a string (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_01\" title=\"Figure&#xa0;16.6.&#xa0;\">Figure\u00a016.6<\/a><span class=\"bold\"><strong>b<\/strong><\/span>). These beads (histone proteins) can move along the string (DNA) and change the structure of the molecule.<\/p>\n<div id=\"m44536-fig-ch16_03_01\" class=\"figure\" title=\"Figure&#xa0;16.6.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44536-fs-id1807369\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155846\/Figure_16_03_01ab.jpg\" width=\"550\" alt=\"Part A depicts a nucleosome composed of spherical histone proteins that are fused together. A double-stranded DNA helix wraps around the nucleosome twice. Free DNA extends from either end of the nucleosome. Part B is an electron micrograph of DNA that is associated with nucleosomes. Each nucleosome looks like a bead. The beads are connected together by free DNA. Nine beads strung together is approximately 150 nm across.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">DNA is folded around histone proteins to create (a) nucleosome complexes. These nucleosomes control the access of proteins to the underlying DNA. When viewed through an electron microscope (b), the nucleosomes look like beads on a string. (credit \u201cmicrograph\u201d: modification of work by Chris Woodcock)<\/div>\n<\/div>\n<p><span id=\"m44536-fs-id1596128\"> <\/span>If DNA encoding a specific gene is to be transcribed into RNA, the nucleosomes surrounding that region of DNA can slide down the DNA to open that specific chromosomal region and allow for the transcriptional machinery (RNA polymerase) to initiate transcription (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xa0;16.7.&#xa0;\">Figure\u00a016.7<\/a>). Nucleosomes can move to open the chromosome structure to expose a segment of DNA, but do so in a very controlled manner.<\/p>\n<div id=\"m44536-fs-id1485526\" class=\"note art-connection\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Art Connection<\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44536-fs-id2020475\"> <\/span><\/p>\n<div id=\"m44536-fig-ch16_03_02\" class=\"figure\" title=\"Figure&#xa0;16.7.&#xa0;\">\n<div class=\"body\"><span class=\"inlinemediaobject\"><span id=\"m44536-fs-id3078242\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155848\/Figure_16_03_02.png\" width=\"450\" alt=\"Nucleosomes are depicted as wheel-like structures. The nucleosomes are made up of histones, and have DNA wrapped around the outside. Each histone has a tail that juts out from the wheel. When DNA and the histone tails are methylated, the nucleosomes pack tightly together so there is no free DNA. Transcription factors cannot bind, and genes are not expressed. Acetylation of histone tails results in a looser packing of the nucleosomes. Free DNA is exposed between the nucleosomes, and transcription factors are able to bind genes on this exposed DNA.\" \/><\/span><\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">Nucleosomes can slide along DNA. When nucleosomes are spaced closely together (top), transcription factors cannot bind and gene expression is turned off. When the nucleosomes are spaced far apart (bottom), the DNA is exposed. Transcription factors can bind, allowing gene expression to occur. Modifications to the histones and DNA affect nucleosome spacing.<\/div>\n<\/div>\n<p><span id=\"m44536-fs-id1236637\"> <\/span>In females, one of the two X chromosomes is inactivated during embryonic development because of epigenetic changes to the chromatin. What impact do you think these changes would have on nucleosome packing?<\/p>\n<\/div>\n<\/div>\n<p><span id=\"m44536-fs-id1509913\"> <\/span>How the histone proteins move is dependent on signals found on both the histone proteins and on the DNA. These signals are tags added to histone proteins and DNA that tell the histones if a chromosomal region should be open or closed (<a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_03\" title=\"Figure&#xa0;16.8.&#xa0;\">Figure\u00a016.8<\/a> depicts modifications to histone proteins and DNA). These tags are not permanent, but may be added or removed as needed. They are chemical modifications (phosphate, methyl, or acetyl groups) that are attached to specific amino acids in the protein or to the nucleotides of the DNA. The tags do not alter the DNA base sequence, but they do alter how tightly wound the DNA is around the histone proteins. DNA is a negatively charged molecule; therefore, changes in the charge of the histone will change how tightly wound the DNA molecule will be. When unmodified, the histone proteins have a large positive charge; by adding chemical modifications like acetyl groups, the charge becomes less positive.<\/p>\n<p><span id=\"m44536-fs-id2261473\"> <\/span>The DNA molecule itself can also be modified. This occurs within very specific regions called CpG islands. These are stretches with a high frequency of cytosine and guanine dinucleotide DNA pairs (CG) found in the promoter regions of genes. When this configuration exists, the cytosine member of the pair can be methylated (a methyl group is added). This modification changes how the DNA interacts with proteins, including the histone proteins that control access to the region. Highly methylated (hypermethylated) DNA regions with deacetylated histones are tightly coiled and transcriptionally inactive.<\/p>\n<div id=\"m44536-fig-ch16_03_03\" class=\"figure\" title=\"Figure&#xa0;16.8.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44536-fs-id2322545\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155850\/Figure_16_03_03.jpg\" width=\"500\" alt=\"Illustration shows a chromosome that is partially unraveled and magnified, revealing histone proteins wound around the DNA double helix. Histones are proteins around which DNA winds for compaction and gene regulation. Methylation of DNA and chemical modification of histone tails are known as epigenetic changes. Epigenetic changes alter the spacing of nucleosomes and change gene expression. Epigenetic changes may result from development, either in utero or in childhood, environmental chemicals, drugs, aging, or diet. Epigenetic changes may result in cancer, autoimmune disease, mental disorders, and diabetes.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.8<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">Histone proteins and DNA nucleotides can be modified chemically. Modifications affect nucleosome spacing and gene expression. (credit: modification of work by NIH)<\/div>\n<\/div>\n<p><span id=\"m44536-fs-id1605467\"> <\/span>This type of gene regulation is called epigenetic regulation. Epigenetic means \u201caround genetics.\u201d The changes that occur to the histone proteins and DNA do not alter the nucleotide sequence and are not permanent. Instead, these changes are temporary (although they often persist through multiple rounds of cell division) and alter the chromosomal structure (open or closed) as needed. A gene can be turned on or off depending upon the location and modifications to the histone proteins and DNA. If a gene is to be transcribed, the histone proteins and DNA are modified surrounding the chromosomal region encoding that gene. This opens the chromosomal region to allow access for RNA polymerase and other proteins, called <em class=\"glossterm\"><span id=\"m44536-autoid-cnx2dbk-id1513751\"> <\/span>transcription factors<\/em><a id=\"id424527\" class=\"indexterm\">, to bind to the promoter region, located just upstream of the gene, and initiate transcription. If a gene is to remain turned off, or silenced, the histone proteins and DNA have different modifications that signal a closed chromosomal configuration. In this closed configuration, the RNA polymerase and transcription factors do not have access to the DNA and transcription cannot occur (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xa0;16.7.&#xa0;\">Figure\u00a016.7<\/a>).<\/p>\n<div id=\"m44536-fs-id1469378\" class=\"note interactive\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div>\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44536-fs-id3096241\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155854\/epigenetic_reg.png\" width=\"120\" alt=\"QR Code representing a URL\" \/><\/div>\n<p><span id=\"m44536-fs-id1724210\"> <\/span>View <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/epigenetic_reg\" target=\"\">this video<\/a> that describes how epigenetic regulation controls gene expression.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div xml:lang=\"en\" class=\"section module\" title=\"16.4.&#xa0;Eukaryotic Transcription Gene Regulation\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<sup><a href=\"co03.html#book-attribution-m44538\">*<\/a><\/sup><\/span><\/span><\/h2>\n<\/div>\n<div class=\"abstract\">\n<div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"><\/span><\/span><\/span><\/div>\n<p>By the end of this section, you will be able to:\n<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">\n<p>Discuss the role of transcription factors in gene regulation<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Explain how enhancers and repressors regulate gene expression<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"toc\">\n<ul>\n<li class=\"toc-section\"><a href=\"#m44538-fs-id1967852\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Promoter and the Transcription Machinery<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44538-fs-id2571418\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Enhancers and Transcription<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44538-fs-id685962\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Turning Genes Off: Transcriptional Repressors<\/span><\/a><\/li>\n<\/ul>\n<\/div>\n<p><span id=\"m44538-fs-id2745728\"> <\/span>Like prokaryotic cells, the transcription of genes in eukaryotes requires the actions of an RNA polymerase to bind to a sequence upstream of a gene to initiate transcription. However, unlike prokaryotic cells, the eukaryotic RNA polymerase requires other proteins, or transcription factors, to facilitate transcription initiation. Transcription factors are proteins that bind to the promoter sequence and other regulatory sequences to control the transcription of the target gene. RNA polymerase by itself cannot initiate transcription in eukaryotic cells. Transcription factors must bind to the promoter region first and recruit RNA polymerase to the site for transcription to be established.<\/p>\n<div id=\"m44538-fs-id2022629\" class=\"note interactive\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div>\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44538-fs-id1595515\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155857\/transcript_RNA.png\" width=\"120\" alt=\"QR Code representing a URL\" \/><\/div>\n<p><span id=\"m44538-fs-id2192558\"> <\/span>View the process of transcription\u2014the making of RNA from a DNA template\u2014at <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/transcript_RNA\" target=\"\">this site<\/a>.<\/p>\n<\/div>\n<\/div>\n<div class=\"section\" title=\"The Promoter and the Transcription Machinery\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44538-fs-id1967852\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Promoter and the Transcription Machinery<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44538-fs-id1645226\"> <\/span>Genes are organized to make the control of gene expression easier. The promoter region is immediately upstream of the coding sequence. This region can be short (only a few nucleotides in length) or quite long (hundreds of nucleotides long). The longer the promoter, the more available space for proteins to bind. This also adds more control to the transcription process. The length of the promoter is gene-specific and can differ dramatically between genes. Consequently, the level of control of gene expression can also differ quite dramatically between genes. The purpose of the promoter is to bind transcription factors that control the initiation of transcription.<\/p>\n<p><span id=\"m44538-fs-id2904783\"> <\/span>Within the promoter region, just upstream of the transcriptional start site, resides the TATA box. This box is simply a repeat of thymine and adenine dinucleotides (literally, TATA repeats). RNA polymerase binds to the transcription initiation complex, allowing transcription to occur. To initiate transcription, a transcription factor (TFIID) is the first to bind to the TATA box. Binding of TFIID recruits other transcription factors, including TFIIB, TFIIE, TFIIF, and TFIIH to the TATA box. Once this complex is assembled, RNA polymerase can bind to its upstream sequence. When bound along with the transcription factors, RNA polymerase is phosphorylated. This releases part of the protein from the DNA to activate the transcription initiation complex and places RNA polymerase in the correct orientation to begin transcription; DNA-bending protein brings the enhancer, which can be quite a distance from the gene, in contact with transcription factors and mediator proteins (<a class=\"xref target-figure\" href=\"ch16.html#m44538-fig-ch16_04_01\" title=\"Figure&#xa0;16.9.&#xa0;\">Figure\u00a016.9<\/a>).<\/p>\n<div id=\"m44538-fig-ch16_04_01\" class=\"figure\" title=\"Figure&#xa0;16.9.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44538-fs-id1778252\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155900\/Figure_16_04_01.jpg\" width=\"320\" alt=\"Eukaryotic gene expression is controlled by a promoter immediately adjacent to the gene, and an enhancer far upstream. The DNA folds over itself, bringing the enhancer next to the promoter. Transcription factors and mediator proteins are sandwiched between the promoter and the enhancer. Short DNA sequences within the enhancer called distal control elements bind activators, which in turn bind transcription factors and mediator proteins bound to the promoter. RNA polymerase binds the complex, allowing transcription to begin. Different genes have enhancers with different distal control elements, allowing differential regulation of transcription.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.9<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">An enhancer is a DNA sequence that promotes transcription. Each enhancer is made up of short DNA sequences called distal control elements. Activators bound to the distal control elements interact with mediator proteins and transcription factors. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.<\/div>\n<\/div>\n<p><span id=\"m44538-fs-id1911410\"> <\/span>In addition to the general transcription factors, other transcription factors can bind to the promoter to regulate gene transcription. These transcription factors bind to the promoters of a specific set of genes. They are not general transcription factors that bind to every promoter complex, but are recruited to a specific sequence on the promoter of a specific gene. There are hundreds of transcription factors in a cell that each bind specifically to a particular DNA sequence motif. When transcription factors bind to the promoter just upstream of the encoded gene, it is referred to as a <em class=\"glossterm\"><span id=\"m44538-autoid-cnx2dbk-id1466670\"> <\/span><span class=\"emphasis\"><em>cis<\/em><\/span>-acting element<\/em><a id=\"id519492\" class=\"indexterm\">, because it is on the same chromosome just next to the gene. The region that a particular transcription factor binds to is called the <em class=\"glossterm\"><span id=\"m44538-autoid-cnx2dbk-id1394712\"> <\/span>transcription factor binding site<\/em><\/a><a id=\"id519508\" class=\"indexterm\">. Transcription factors respond to environmental stimuli that cause the proteins to find their binding sites and initiate transcription of the gene that is needed.<\/a><\/p>\n<\/div>\n<div class=\"section\" title=\"Enhancers and Transcription\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44538-fs-id2571418\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Enhancers and Transcription<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44538-fs-id2700899\"> <\/span>In some eukaryotic genes, there are regions that help increase or enhance transcription. These regions, called <em class=\"glossterm\"><span id=\"m44538-autoid-cnx2dbk-id1394731\"> <\/span>enhancers<\/em><a id=\"id519533\" class=\"indexterm\">, are not necessarily close to the genes they enhance. They can be located upstream of a gene, within the coding region of the gene, downstream of a gene, or may be thousands of nucleotides away.<\/a><\/p>\n<p><span id=\"m44538-fs-id2373880\"> <\/span>Enhancer regions are binding sequences, or sites, for transcription factors. When a DNA-bending protein binds, the shape of the DNA changes (<a class=\"xref target-figure\" href=\"ch16.html#m44538-fig-ch16_04_01\" title=\"Figure&#xa0;16.9.&#xa0;\">Figure\u00a016.9<\/a>). This shape change allows for the interaction of the activators bound to the enhancers with the transcription factors bound to the promoter region and the RNA polymerase. Whereas DNA is generally depicted as a straight line in two dimensions, it is actually a three-dimensional object. Therefore, a nucleotide sequence thousands of nucleotides away can fold over and interact with a specific promoter.<\/p>\n<\/div>\n<div class=\"section\" title=\"Turning Genes Off: Transcriptional Repressors\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44538-fs-id685962\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Turning Genes Off: Transcriptional Repressors<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44538-fs-id1797856\"> <\/span>Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli to prevent the binding of activating transcription factors.<\/p>\n<\/div>\n<\/div>\n<div xml:lang=\"en\" class=\"section module\" title=\"16.5.&#xa0;Eukaryotic Post-transcriptional Gene Regulation\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<sup><a href=\"co03.html#book-attribution-m44539\">*<\/a><\/sup><\/span><\/span><\/h2>\n<\/div>\n<div class=\"abstract\">\n<div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"><\/span><\/span><\/span><\/div>\n<p>By the end of this section, you will be able to:\n<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">\n<p>Understand RNA splicing and explain its role in regulating gene expression<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Describe the importance of RNA stability in gene regulation<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"toc\">\n<ul>\n<li class=\"toc-section\"><a href=\"#m44539-fs-id2019050\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA splicing, the first stage of post-transcriptional control<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44539-fs-id3071072\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Control of RNA Stability<\/span><\/a>\n<ul>\n<li class=\"toc-section\"><a href=\"#m44539-fs-id2590621\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA Stability and microRNAs<\/span><\/a><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/div>\n<p><span id=\"m44539-fs-id2098364\"> <\/span>RNA is transcribed, but must be processed into a mature form before translation can begin. This processing after an RNA molecule has been transcribed, but before it is translated into a protein, is called post-transcriptional modification. As with the epigenetic and transcriptional stages of processing, this post-transcriptional step can also be regulated to control gene expression in the cell. If the RNA is not processed, shuttled, or translated, then no protein will be synthesized.<\/p>\n<div class=\"section\" title=\"RNA splicing, the first stage of post-transcriptional control\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44539-fs-id2019050\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA splicing, the first stage of post-transcriptional control<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44539-fs-id1899262\"> <\/span>In eukaryotic cells, the RNA transcript often contains regions, called introns, that are removed prior to translation. The regions of RNA that code for protein are called exons (<a class=\"xref target-figure\" href=\"ch16.html#m44539-fig-ch16_05_01\" title=\"Figure&#xa0;16.10.&#xa0;\">Figure\u00a016.10<\/a>). After an RNA molecule has been transcribed, but prior to its departure from the nucleus to be translated, the RNA is processed and the introns are removed by splicing.<\/p>\n<div id=\"m44539-fig-ch16_05_01\" class=\"figure\" title=\"Figure&#xa0;16.10.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44539-fs-id1770169\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155902\/Figure_16_05_03.jpg\" width=\"400\" alt=\"A pre-mRNA has four exons separated by three introns. The pre-mRNA can be alternatively spliced to create two different proteins, each with three exons. One protein contains exons one, two, and three. The other protein contains exons one, three and four.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.10<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">Pre-mRNA can be alternatively spliced to create different proteins.<\/div>\n<\/div>\n<div id=\"m44539-fs-id2048195\" class=\"note evolution\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Evolution Connection<\/span><\/div>\n<div class=\"body\">\n<p title=\"Alternative RNA Splicing\"><span id=\"m44539-fs-id1418200\"> <\/span><\/p>\n<div class=\"title\"><b>Alternative RNA Splicing<\/b><\/div>\n<p title=\"Alternative RNA Splicing\">In the 1970s, genes were first observed that exhibited alternative RNA splicing. Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of introns, and sometimes exons, are removed from the transcript (<a class=\"xref target-figure\" href=\"ch16.html#m44539-fig-ch16_05_02\" title=\"Figure&#xa0;16.11.&#xa0;\">Figure\u00a016.11<\/a>). This alternative splicing can be haphazard, but more often it is controlled and acts as a mechanism of gene regulation, with the frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development. Alternative splicing is now understood to be a common mechanism of gene regulation in eukaryotes; according to one estimate, 70 percent of genes in humans are expressed as multiple proteins through alternative splicing.<\/p>\n<div id=\"m44539-fig-ch16_05_02\" class=\"figure\" title=\"Figure&#xa0;16.11.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44539-fs-id2194968\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155905\/Figure_15_04_02.jpg\" width=\"400\" alt=\"Diagram shows five methods of alternative splicing of pre-mRNA. When exon skipping occurs, an exon is spliced out in one mature mRNA product and retained in another. When mutually exclusive exons are present in the pre-mRNA, only one is retained in the mature mRNA. When an alternative 5&#x2019; donor site is present, the location of the 5&#x2019; splice site is variable. When an alternative 3&#x2019; acceptor site is present, the location of the 3&#x2019; splice site is variable. Intron retention results in an intron being retained in one mature mRNA and spliced out in another.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.11<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">There are five basic modes of alternative splicing.<\/div>\n<\/div>\n<p><span id=\"m44539-fs-id1770543\"> <\/span>How could alternative splicing evolve? Introns have a beginning and ending recognition sequence; it is easy to imagine the failure of the splicing mechanism to identify the end of an intron and instead find the end of the next intron, thus removing two introns and the intervening exon. In fact, there are mechanisms in place to prevent such intron skipping, but mutations are likely to lead to their failure. Such \u201cmistakes\u201d would more than likely produce a nonfunctional protein. Indeed, the cause of many genetic diseases is alternative splicing rather than mutations in a sequence. However, alternative splicing would create a protein variant without the loss of the original protein, opening up possibilities for adaptation of the new variant to new functions. Gene duplication has played an important role in the evolution of new functions in a similar way by providing genes that may evolve without eliminating the original, functional protein.<\/p>\n<\/div>\n<\/div>\n<div id=\"m44539-fs-id2030028\" class=\"note interactive\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div>\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44539-fs-id2004529\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155908\/mRNA_splicing.png\" width=\"120\" alt=\"QR Code representing a URL\" \/><\/div>\n<p><span id=\"m44539-fs-id2571418\"> <\/span>Visualize how mRNA splicing happens by watching the process in action in <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/mRNA_splicing\" target=\"\">this video<\/a>.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\" title=\"Control of RNA Stability\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44539-fs-id3071072\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Control of RNA Stability<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44539-fs-id1703747\"> <\/span>Before the mRNA leaves the nucleus, it is given two protective &#8220;caps&#8221; that prevent the end of the strand from degrading during its journey. The <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578035\"> <\/span>5&#8242; cap<\/em><a id=\"id520137\" class=\"indexterm\">, which is placed on the 5&#8242; end of the mRNA, is usually composed of a methylated guanosine triphosphate molecule (GTP). The  <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578040\"> <\/span>poly-A tail<\/em><\/a><a id=\"id520148\" class=\"indexterm\">, which is attached to the 3&#8242; end, is usually composed of a series of adenine nucleotides. Once the RNA is transported to the cytoplasm, the length of time that the RNA resides there can be controlled. Each RNA molecule has a defined lifespan and decays at a specific rate. This rate of decay can influence how much protein is in the cell. If the decay rate is increased, the RNA will not exist in the cytoplasm as long, shortening the time for translation to occur. Conversely, if the rate of decay is decreased, the RNA molecule will reside in the cytoplasm longer and more protein can be translated. This rate of decay is referred to as the RNA stability. If the RNA is stable, it will be detected for longer periods of time in the cytoplasm.<\/a><\/p>\n<p><span id=\"m44539-fs-id2167834\"> <\/span>Binding of proteins to the RNA can influence its stability. Proteins, called <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578056\"> <\/span>RNA-binding proteins<\/em><a id=\"id520170\" class=\"indexterm\">, or RBPs, can bind to the regions of the RNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578061\"> <\/span>untranslated regions<\/em><\/a><a id=\"id520182\" class=\"indexterm\">, or UTRs. They are not introns (those have been removed in the nucleus). Rather, these are regions that regulate mRNA localization, stability, and protein translation. The region just before the protein-coding region is called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578067\"> <\/span>5&#8242; UTR<\/em><\/a><a id=\"id520194\" class=\"indexterm\">, whereas the region after the coding region is called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1578070\"> <\/span>3&#8242; UTR<\/em><\/a><a id=\"id520206\" class=\"indexterm\"> (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44539-fig-ch16_05_03\" title=\"Figure&#xa0;16.12.&#xa0;\">Figure\u00a016.12<\/a>). The binding of RBPs to these regions can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.<\/p>\n<div id=\"m44539-fig-ch16_05_03\" class=\"figure\" title=\"Figure&#xa0;16.12.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44539-fs-id1445473\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155910\/Figure_16_05_02.jpg\" width=\"450\" alt=\"In the mature RNA molecule, exons are spliced together between the 5' and 3' untranslated regions. A 5' cap is attached to the 5' untranslated region, and a poly-A tail is attached to the 3' untranslated region. RNA-binding proteins associate with the 5' and 3' untranslated regions.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.12<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">The protein-coding region of mRNA is flanked by 5&#8242; and 3&#8242; untranslated regions (UTRs). The presence of RNA-binding proteins at the 5&#8242; or 3&#8242; UTR influences the stability of the RNA molecule.<\/div>\n<\/div>\n<div class=\"section\" title=\"RNA Stability and microRNAs\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h4 id=\"m44539-fs-id2590621\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">RNA Stability and microRNAs<\/span><\/span><\/h4>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44539-fs-id1550134\"> <\/span>In addition to RBPs that bind to and control (increase or decrease) RNA stability, other elements called microRNAs can bind to the RNA molecule. These <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1598074\"> <\/span>microRNAs<\/em><a id=\"id520265\" class=\"indexterm\">, or miRNAs, are short RNA molecules that are only 21\u201324 nucleotides in length. The miRNAs are made in the nucleus as longer pre-miRNAs. These pre-miRNAs are chopped into mature miRNAs by a protein called <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1624188\"> <\/span>dicer<\/em><\/a><a id=\"id520280\" class=\"indexterm\">. Like transcription factors and RBPs, mature miRNAs recognize a specific sequence and bind to the RNA; however, miRNAs also associate with a ribonucleoprotein complex called the <em class=\"glossterm\"><span id=\"m44539-autoid-cnx2dbk-id1624193\"> <\/span>RNA-induced silencing complex (RISC)<\/em><\/a><a id=\"id520292\" class=\"indexterm\">. RISC binds along with the miRNA to degrade the target mRNA. Together, miRNAs and the RISC complex rapidly destroy the RNA molecule.<\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n<div xml:lang=\"en\" class=\"section module\" title=\"16.6.&#xa0;Eukaryotic Translational and Post-translational Gene Regulation\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<sup><a href=\"co03.html#book-attribution-m44542\">*<\/a><\/sup><\/span><\/span><\/h2>\n<\/div>\n<div class=\"abstract\">\n<div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"><\/span><\/span><\/span><\/div>\n<p>By the end of this section, you will be able to:\n<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">\n<p>Understand the process of translation and discuss its key factors<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Describe how the initiation complex controls translation<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Explain the different ways in which the post-translational control of gene expression takes place<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"toc\">\n<ul>\n<li class=\"toc-section\"><a href=\"#m44542-fs-id1396738\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Initiation Complex and Translation Rate<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44542-fs-id1956507\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Chemical Modifications, Protein Activity, and Longevity<\/span><\/a><\/li>\n<\/ul>\n<\/div>\n<p><span id=\"m44542-fs-id1976887\"> <\/span>After the RNA has been transported to the cytoplasm, it is translated into protein. Control of this process is largely dependent on the RNA molecule. As previously discussed, the stability of the RNA will have a large impact on its translation into a protein. As the stability changes, the amount of time that it is available for translation also changes.<\/p>\n<div class=\"section\" title=\"The Initiation Complex and Translation Rate\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44542-fs-id1396738\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">The Initiation Complex and Translation Rate<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44542-fs-id2754887\"> <\/span>Like transcription, translation is controlled by proteins that bind and initiate the process. In translation, the complex that assembles to start the process is referred to as the <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302722\"> <\/span>initiation complex<\/em><a id=\"id520685\" class=\"indexterm\">. The first protein to bind to the RNA to initiate translation is the <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302725\"> <\/span>eukaryotic initiation factor-2 (eIF-2)<\/em><\/a><a id=\"id520696\" class=\"indexterm\">. The eIF-2 protein is active when it binds to the high-energy molecule <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302729\"> <\/span>guanosine triphosphate (GTP)<\/em><\/a><a id=\"id520707\" class=\"indexterm\">. GTP provides the energy to start the reaction by giving up a phosphate and becoming <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302733\"> <\/span>guanosine diphosphate (GDP)<\/em><\/a><a id=\"id520718\" class=\"indexterm\">. The eIF-2 protein bound to GTP binds to the small <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302737\"> <\/span>40S ribosomal subunit<\/em><\/a><a id=\"id520728\" class=\"indexterm\">. When bound, the methionine initiator tRNA associates with the eIF-2\/40S ribosome complex, bringing along with it the mRNA to be translated. At this point, when the initiator complex is assembled, the GTP is converted into GDP and energy is released. The phosphate and the eIF-2 protein are released from the complex and the large <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1302743\"> <\/span>60S ribosomal subunit<\/em><\/a><a id=\"id520742\" class=\"indexterm\"> binds to translate the RNA. The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly and translation is impeded (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xa0;16.13.&#xa0;\">Figure\u00a016.13<\/a>). When eIF-2 remains unphosphorylated, it binds the RNA and actively translates the protein.<\/p>\n<div id=\"m44542-fs-id2339240\" class=\"note art-connection\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Art Connection<\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44542-fs-id2250537\"> <\/span>\n<\/p>\n<div id=\"m44542-fig-ch16_06_01\" class=\"figure\" title=\"Figure&#xa0;16.13.&#xa0;\">\n<div class=\"body\"><span class=\"inlinemediaobject\"><span id=\"m44542-fs-id1453957\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155913\/Figure_16_06_01.png\" width=\"320\" alt=\"The eIF2 protein is a translation factor that binds to the small 40S ribosome subunit. When eIF2 is phosphorylated, translation is blocked.\" \/><\/span><\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.13<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">Gene expression can be controlled by factors that bind the translation initiation complex.<\/div>\n<\/div>\n<p><span id=\"m44542-fs-id1770367\"> <\/span>An increase in phosphorylation levels of eIF-2 has been observed in patients with neurodegenerative diseases such as Alzheimer\u2019s, Parkinson\u2019s, and Huntington\u2019s. What impact do you think this might have on protein synthesis?<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\" title=\"Chemical Modifications, Protein Activity, and Longevity\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44542-fs-id1956507\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Chemical Modifications, Protein Activity, and Longevity<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44542-fs-id3321766\"> <\/span>Proteins can be chemically modified with the addition of groups including methyl, phosphate, acetyl, and ubiquitin groups. The addition or removal of these groups from proteins regulates their activity or the length of time they exist in the cell. Sometimes these modifications can regulate where a protein is found in the cell\u2014for example, in the nucleus, the cytoplasm, or attached to the plasma membrane.<\/p>\n<p><span id=\"m44542-fs-id2080792\"> <\/span>Chemical modifications occur in response to external stimuli such as stress, the lack of nutrients, heat, or ultraviolet light exposure. These changes can alter epigenetic accessibility, transcription, mRNA stability, or translation\u2014all resulting in changes in expression of various genes. This is an efficient way for the cell to rapidly change the levels of specific proteins in response to the environment.  Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).<\/p>\n<p><span id=\"m44542-fs-id3327902\"> <\/span> The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the <em class=\"glossterm\"><span id=\"m44542-autoid-cnx2dbk-id1421910\"> <\/span>proteasome<\/em><a id=\"id520859\" class=\"indexterm\">, an organelle that functions to remove proteins, to be degraded (<\/a><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_02\" title=\"Figure&#xa0;16.14.&#xa0;\">Figure\u00a016.14<\/a>). One way to control gene expression, therefore, is to alter the longevity of the protein.<\/p>\n<div id=\"m44542-fig-ch16_06_02\" class=\"figure\" title=\"Figure&#xa0;16.14.&#xa0;\">\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44542-fs-id2304651\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155916\/Figure_16_06_02.jpg\" width=\"350\" alt=\"Multiple ubiquitin groups bind to a protein. The tagged protein is then fed into the hollow tube of a proteasome. The proteasome degrades the protein.\" \/><\/div>\n<\/div>\n<div class=\"title\"><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">Figure\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-n\">16.14<\/span><span class=\"cnx-gentext-figure cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-figure cnx-gentext-t\"><\/span><\/div>\n<div class=\"caption\">Proteins with ubiquitin tags are marked for degradation within the proteasome.<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div xml:lang=\"en\" class=\"section module\" title=\"16.7.&#xa0;Cancer and Gene Regulation\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<sup><a href=\"co03.html#book-attribution-m44548\">*<\/a><\/sup><\/span><\/span><\/h2>\n<\/div>\n<div class=\"abstract\">\n<div class=\"title\"><span><span class=\"cnx-gentext-abstract cnx-gentext-autogenerated\"><span class=\"cnx-gentext-abstract cnx-gentext-t\"><\/span><\/span><\/span><\/div>\n<p>By the end of this section, you will be able to:\n<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">\n<p>Describe how changes to gene expression can cause cancer<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Explain how changes to gene expression at different levels can disrupt the cell cycle<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>Discuss how understanding regulation of gene expression can lead to better drug design<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"toc\">\n<ul>\n<li class=\"toc-section\"><a href=\"#m44548-fs-id1775261\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer: Disease of Altered Gene Expression<\/span><\/a>\n<ul>\n<li class=\"toc-section\"><a href=\"#m44548-fs-id1787656\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Tumor Suppressor Genes, Oncogenes, and Cancer<\/span><\/a><\/li>\n<\/ul>\n<\/li>\n<li class=\"toc-section\"><a href=\"#m44548-fs-id2570388\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Epigenetic Alterations<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44548-fs-id1977751\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Transcriptional Control<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44548-fs-id2749879\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Post-transcriptional Control<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44548-fs-id1988417\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Translational\/Post-translational Control<\/span><\/a><\/li>\n<li class=\"toc-section\"><a href=\"#m44548-fs-idp254559760\" class=\"target-section\"><span class=\"cnx-gentext-section cnx-gentext-t\">New Drugs to Combat Cancer: Targeted Therapies<\/span><\/a><\/li>\n<\/ul>\n<\/div>\n<p><span id=\"m44548-fs-id2905050\"> <\/span>Cancer is not a single disease but includes many different diseases.  In cancer cells, mutations modify cell-cycle control and cells don\u2019t stop growing as they normally would. Mutations can also alter the growth rate or the progression of the cell through the cell cycle. One example of a gene modification that alters the growth rate is increased phosphorylation of cyclin B, a protein that controls the progression of a cell through the cell cycle and serves as a cell-cycle checkpoint protein.<\/p>\n<p><span id=\"m44548-fs-id2337886\"> <\/span>For cells to move through each phase of the cell cycle, the cell must pass through checkpoints. This ensures that the cell has properly completed the step and has not encountered any mutation that will alter its function. Many proteins, including cyclin B, control these checkpoints. The phosphorylation of cyclin B, a post-translational event, alters its function. As a result, cells can progress through the cell cycle unimpeded, even if mutations exist in the cell and its growth should be terminated. This post-translational change of cyclin B prevents it from controlling the cell cycle and contributes to the development of cancer.<\/p>\n<div class=\"section\" title=\"Cancer: Disease of Altered Gene Expression\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44548-fs-id1775261\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer: Disease of Altered Gene Expression<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id1772073\"> <\/span>Cancer can be described as a disease of altered gene expression. There are many proteins that are turned on or off (gene activation or gene silencing) that dramatically alter the overall activity of the cell. A gene that is not normally expressed in that cell can be switched on and expressed at high levels. This can be the result of gene mutation or changes in gene regulation (epigenetic, transcription, post-transcription, translation, or post-translation).<\/p>\n<p><span id=\"m44548-fs-id1568624\"> <\/span>Changes in epigenetic regulation, transcription, RNA stability, protein translation, and post-translational control can be detected in cancer. While these changes don\u2019t occur simultaneously in one cancer, changes at each of these levels can be detected when observing cancer at different sites in different individuals. Therefore, changes in <em class=\"glossterm\"><span id=\"m44548-autoid-cnx2dbk-id1414218\"> <\/span>histone acetylation<\/em><a id=\"id521318\" class=\"indexterm\"> (epigenetic modification that leads to gene silencing), activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification can all be detected at some point in various cancer cells. Scientists are working to understand the common changes that give rise to certain types of cancer or how a modification might be exploited to destroy a tumor cell.<\/a><\/p>\n<div class=\"section\" title=\"Tumor Suppressor Genes, Oncogenes, and Cancer\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h4 id=\"m44548-fs-id1787656\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Tumor Suppressor Genes, Oncogenes, and Cancer<\/span><\/span><\/h4>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id1524784\"> <\/span>In normal cells, some genes function to prevent excess, inappropriate cell growth. These are tumor suppressor genes, which are active in normal cells to prevent uncontrolled cell growth. There are many tumor suppressor genes in cells. The most studied tumor suppressor gene is p53, which is mutated in over 50 percent of all cancer types.  The p53 protein itself functions as a transcription factor. It can bind to sites in the promoters of genes to initiate transcription. Therefore, the mutation of p53 in cancer will dramatically alter the transcriptional activity of its target genes.<\/p>\n<div id=\"m44548-fs-id1687530\" class=\"note interactive\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Link to Learning<\/span><\/div>\n<div class=\"body\">\n<div class=\"mediaobject\"><span id=\"m44548-fs-id2334394\"> <\/span><img decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/511\/2016\/08\/19155919\/p53_cancer.png\" width=\"120\" alt=\"QR Code representing a URL\" \/><\/div>\n<p><span id=\"m44548-fs-id2126300\"> <\/span>Watch <a class=\"link\" href=\"http:\/\/openstaxcollege.org\/l\/p53_cancer\" target=\"\">this animation<\/a> to learn more about the use of p53 in fighting cancer.<\/p>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id1461234\"> <\/span>Proto-oncogenes are positive cell-cycle regulators. When mutated, proto-oncogenes can become oncogenes and cause cancer. Overexpression of the oncogene can lead to uncontrolled cell growth. This is because oncogenes can alter transcriptional activity, stability, or protein translation of another gene that directly or indirectly controls cell growth. An example of an oncogene involved in cancer is a protein called myc. <em class=\"glossterm\"><span id=\"m44548-autoid-cnx2dbk-id1439919\"> <\/span>Myc<\/em><a id=\"id521401\" class=\"indexterm\"> is a transcription factor that is aberrantly activated in Burkett\u2019s Lymphoma, a cancer of the lymph system. Overexpression of myc transforms normal B cells into cancerous cells that continue to grow uncontrollably. High B-cell numbers can result in tumors that can interfere with normal bodily function. Patients with Burkett\u2019s lymphoma can develop tumors on their jaw or in their mouth that interfere with the ability to eat.<\/a><\/p>\n<\/div>\n<\/div>\n<div class=\"section\" title=\"Cancer and Epigenetic Alterations\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44548-fs-id2570388\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Epigenetic Alterations<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id1675964\"> <\/span>Silencing genes through epigenetic mechanisms is also very common in cancer cells. There are characteristic modifications to histone proteins and DNA that are associated with silenced genes. In cancer cells, the DNA in the promoter region of silenced genes is methylated on cytosine DNA residues in CpG islands. Histone proteins that surround that region lack the acetylation modification that is present when the genes are expressed in normal cells. This combination of DNA methylation and histone deacetylation (epigenetic modifications that lead to gene silencing) is commonly found in cancer. When these modifications occur, the gene present in that chromosomal region is silenced. Increasingly, scientists understand how epigenetic changes are altered in cancer. Because these changes are temporary and can be reversed\u2014for example, by preventing the action of the histone deacetylase protein that removes acetyl groups, or by DNA methyl transferase enzymes that add methyl groups to cytosines in DNA\u2014it is possible to design new drugs and new therapies to take advantage of the reversible nature of these processes. Indeed, many researchers are testing how a silenced gene can be switched back on in a cancer cell to help re-establish normal growth patterns.<\/p>\n<p><span id=\"m44548-fs-id1958502\"> <\/span>Genes involved in the development of many other illnesses, ranging from allergies to inflammation to autism, are thought to be regulated by epigenetic mechanisms. As our knowledge of how genes are controlled deepens, new ways to treat diseases like cancer will emerge.<\/p>\n<\/div>\n<div class=\"section\" title=\"Cancer and Transcriptional Control\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44548-fs-id1977751\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Transcriptional Control<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id2688570\"> <\/span>Alterations in cells that give rise to cancer can affect the transcriptional control of gene expression. Mutations that activate transcription factors, such as increased phosphorylation, can increase the binding of a transcription factor to its binding site in a promoter. This could lead to increased transcriptional activation of that gene that results in modified cell growth. Alternatively, a mutation in the DNA of a promoter or enhancer region can increase the binding ability of a transcription factor. This could also lead to the increased transcription and aberrant gene expression that is seen in cancer cells.<\/p>\n<p><span id=\"m44548-fs-id2971281\"> <\/span>Researchers have been investigating how to control the transcriptional activation of gene expression in cancer. Identifying how a transcription factor binds, or a pathway that activates where a gene can be turned off, has led to new drugs and new ways to treat cancer. In breast cancer, for example, many proteins are overexpressed. This can lead to increased phosphorylation of key transcription factors that increase transcription. One such example is the overexpression of the epidermal growth factor receptor (EGFR) in a subset of breast cancers. The EGFR pathway activates many protein kinases that, in turn, activate many transcription factors that control genes involved in cell growth. New drugs that prevent the activation of EGFR have been developed and are used to treat these cancers.<\/p>\n<\/div>\n<div class=\"section\" title=\"Cancer and Post-transcriptional Control\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44548-fs-id2749879\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Post-transcriptional Control<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id2595766\"> <\/span>Changes in the post-transcriptional control of a gene can also result in cancer. Recently, several groups of researchers have shown that specific cancers have altered expression of miRNAs. Because miRNAs bind to the 3&#8242; UTR of RNA molecules to degrade them, overexpression of these miRNAs could be detrimental to normal cellular activity. Too many miRNAs could dramatically decrease the RNA population leading to a decrease in protein expression. Several studies have demonstrated a change in the miRNA population in specific cancer types. It appears that the subset of miRNAs expressed in breast cancer cells is quite different from the subset expressed in lung cancer cells or even from normal breast cells. This suggests that alterations in miRNA activity can contribute to the growth of breast cancer cells. These types of studies also suggest that if some miRNAs are specifically expressed only in cancer cells, they could be potential drug targets. It would, therefore, be conceivable that new drugs that turn off miRNA expression in cancer could be an effective method to treat cancer.<\/p>\n<\/div>\n<div class=\"section\" title=\"Cancer and Translational\/Post-translational Control\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44548-fs-id1988417\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Translational\/Post-translational Control<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id1953887\"> <\/span>There are many examples of how translational or post-translational modifications of proteins arise in cancer. Modifications are found in cancer cells from the increased translation of a protein to changes in protein phosphorylation to alternative splice variants of a protein. An example of how the expression of an alternative form of a protein can have dramatically different outcomes is seen in colon cancer cells. The c-Flip protein, a protein involved in mediating the cell death pathway, comes in two forms: long (c-FLIPL) and short (c-FLIPS). Both forms appear to be involved in initiating controlled cell death mechanisms in normal cells. However, in colon cancer cells, expression of the long form results in increased cell growth instead of cell death. Clearly, the expression of the wrong protein dramatically alters cell function and contributes to the development of cancer.<\/p>\n<\/div>\n<div class=\"section\" title=\"New Drugs to Combat Cancer: Targeted Therapies\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h3 id=\"m44548-fs-idp254559760\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">New Drugs to Combat Cancer: Targeted Therapies<\/span><\/span><\/h3>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44548-fs-id1812931\"> <\/span>Scientists are using what is known about the regulation of gene expression in disease states, including cancer, to develop new ways to treat and prevent disease development. Many scientists are designing drugs on the basis of the gene expression patterns within individual tumors. This idea, that therapy and medicines can be tailored to an individual, has given rise to the field of personalized medicine. With an increased understanding of gene regulation and gene function, medicines can be designed to specifically target diseased cells without harming healthy cells. Some new medicines, called targeted therapies, have exploited the overexpression of a specific protein or the mutation of a gene to develop a new medication to treat disease. One such example is the use of anti-EGF receptor medications to treat the subset of breast cancer tumors that have very high levels of the EGF protein. Undoubtedly, more targeted therapies will be developed as scientists learn more about how gene expression changes can cause cancer.<\/p>\n<div id=\"m44548-fs-id2681687\" class=\"note career\">\n<div class=\"title\"><span class=\"cnx-gentext-tip-t\">Career Connection<\/span><\/div>\n<div class=\"body\">\n<p title=\"Clinical Trial Coordinator\"><span id=\"m44548-fs-id1876201\"> <\/span><\/p>\n<div class=\"title\"><b>Clinical Trial Coordinator<\/b><\/div>\n<p title=\"Clinical Trial Coordinator\">A clinical trial coordinator is the person managing the proceedings of the clinical trial. This job includes coordinating patient schedules and appointments, maintaining detailed notes, building the database to track patients (especially for long-term follow-up studies), ensuring proper documentation has been acquired and accepted, and working with the nurses and doctors to facilitate the trial and publication of the results. A clinical trial coordinator may have a science background, like a nursing degree, or other certification. People who have worked in science labs or in clinical offices are also qualified to become a clinical trial coordinator. These jobs are generally in hospitals; however, some clinics and doctor\u2019s offices also conduct clinical trials and may hire a coordinator.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"glossary\" title=\"Glossary\" id=\"id521800\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 class=\"title\"><span class=\"cnx-gentext-glossary cnx-gentext-autogenerated\"><span class=\"cnx-gentext-glossary cnx-gentext-t\">Glossary<\/span><\/span><\/h2>\n<\/div>\n<\/div>\n<\/div>\n<dl>\n<dt><span class=\"emphasis\"><em>cis<\/em><\/span>-acting element<\/dt>\n<dd>\n<p>transcription factor binding sites within the promoter that regulate the transcription of a gene adjacent to it<\/p>\n<\/dd>\n<dt><span class=\"emphasis\"><em>trans<\/em><\/span>-acting element<\/dt>\n<dd>\n<p>transcription factor binding site found outside the promoter or on another chromosome that influences the transcription of a particular gene<\/p>\n<\/dd>\n<dt>3&#8242; UTR<\/dt>\n<dd>\n<p>3&#8242; untranslated region; region just downstream of the protein-coding region in an RNA molecule that is not translated<\/p>\n<\/dd>\n<dt>5&#8242; UTR<\/dt>\n<dd>\n<p>5&#8242; untranslated region; region just upstream of the protein-coding region in an RNA molecule that is not translated<\/p>\n<\/dd>\n<dt>5&#8242; cap<\/dt>\n<dd>\n<p>a methylated guanosine triphosphate (GTP) molecule that is attached to the 5&#8242; end of a messenger RNA to protect the end from degradation<\/p>\n<\/dd>\n<dt>activator<\/dt>\n<dd>\n<p>protein that binds to prokaryotic operators to increase transcription<\/p>\n<\/dd>\n<dt>catabolite activator protein (CAP)<\/dt>\n<dd>\n<p>protein that complexes with cAMP to bind to the promoter sequences of operons that control sugar processing when glucose is not available<\/p>\n<\/dd>\n<dt>DNA methylation<\/dt>\n<dd>\n<p>epigenetic modification that leads to gene silencing; commonly found in cancer cells<\/p>\n<\/dd>\n<dt>dicer<\/dt>\n<dd>\n<p>enzyme that chops the pre-miRNA into the mature form of the miRNA<\/p>\n<\/dd>\n<dt>enhancer<\/dt>\n<dd>\n<p>segment of DNA that is upstream, downstream, perhaps thousands of nucleotides away, or on another chromosome that influence the transcription of a specific gene<\/p>\n<\/dd>\n<dt>epigenetic<\/dt>\n<dd>\n<p>heritable changes that do not involve changes in the DNA sequence<\/p>\n<\/dd>\n<dt>eukaryotic initiation factor-2 (eIF-2)<\/dt>\n<dd>\n<p>protein that binds first to an mRNA to initiate translation<\/p>\n<\/dd>\n<dt>gene expression<\/dt>\n<dd>\n<p>processes that control the turning on or turning off of a gene<\/p>\n<\/dd>\n<dt>guanine diphosphate (GDP)<\/dt>\n<dd>\n<p> molecule that is left after the energy is used to start translation<\/p>\n<\/dd>\n<dt>guanine triphosphate (GTP)<\/dt>\n<dd>\n<p>energy-providing molecule that binds to eIF-2 and is needed for translation<\/p>\n<\/dd>\n<dt>histone acetylation<\/dt>\n<dd>\n<p>epigenetic modification that leads to gene silencing; commonly found in cancer cells found in cancer cells<\/p>\n<\/dd>\n<dt>inducible operon<\/dt>\n<dd>\n<p>operon that can be activated or repressed depending on cellular needs and the surrounding environment<\/p>\n<\/dd>\n<dt>initiation complex<\/dt>\n<dd>\n<p>protein complex containing eIF2-2 that starts translation<\/p>\n<\/dd>\n<dt>lac operon<\/dt>\n<dd>\n<p>operon in prokaryotic cells that encodes genes required for processing and intake of lactose<\/p>\n<\/dd>\n<dt>large 60S ribosomal subunit<\/dt>\n<dd>\n<p>second, larger ribosomal subunit that binds to the RNA to translate it into protein<\/p>\n<\/dd>\n<dt>microRNA (miRNA)<\/dt>\n<dd>\n<p>small RNA molecules (approximately 21 nucleotides in length) that bind to RNA molecules to degrade them<\/p>\n<\/dd>\n<dt>myc<\/dt>\n<dd>\n<p>oncogene that causes cancer in many cancer cells<\/p>\n<\/dd>\n<dt>negative regulator<\/dt>\n<dd>\n<p>protein that prevents transcription<\/p>\n<\/dd>\n<dt>operator<\/dt>\n<dd>\n<p>region of DNA outside of the promoter region that binds activators or repressors that control gene expression in prokaryotic cells<\/p>\n<\/dd>\n<dt>operon<\/dt>\n<dd>\n<p>collection of genes involved in a pathway that are transcribed together as a single mRNA in prokaryotic cells<\/p>\n<\/dd>\n<dt>poly-A tail<\/dt>\n<dd>\n<p>a series of adenine nucleotides that are attached to the 3&#8242; end of an mRNA to protect the end from degradation<\/p>\n<\/dd>\n<dt>positive regulator<\/dt>\n<dd>\n<p>protein that increases transcription<\/p>\n<\/dd>\n<dt>post-transcriptional<\/dt>\n<dd>\n<p>control of gene expression after the RNA molecule has been created but before it is translated into protein<\/p>\n<\/dd>\n<dt>post-translational<\/dt>\n<dd>\n<p>control of gene expression after a protein has been created<\/p>\n<\/dd>\n<dt>proteasome<\/dt>\n<dd>\n<p>organelle that degrades proteins<\/p>\n<\/dd>\n<dt>RISC<\/dt>\n<dd>\n<p>protein complex that binds along with the miRNA to the RNA to degrade it<\/p>\n<\/dd>\n<dt>RNA stability<\/dt>\n<dd>\n<p>how long an RNA molecule will remain intact in the cytoplasm<\/p>\n<\/dd>\n<dt>RNA-binding protein (RBP)<\/dt>\n<dd>\n<p>protein that binds to the 3&#8242; or 5&#8242; UTR to increase or decrease the RNA stability<\/p>\n<\/dd>\n<dt>repressor<\/dt>\n<dd>\n<p>protein that binds to the operator of prokaryotic genes to prevent transcription<\/p>\n<\/dd>\n<dt>small 40S ribosomal subunit<\/dt>\n<dd>\n<p>ribosomal subunit that binds to the RNA to translate it into protein<\/p>\n<\/dd>\n<dt>transcription factor binding site<\/dt>\n<dd>\n<p>sequence of DNA to which a transcription factor binds<\/p>\n<\/dd>\n<dt>transcription factor<\/dt>\n<dd>\n<p>protein that binds to the DNA at the promoter or enhancer region and that influences transcription of a gene<\/p>\n<\/dd>\n<dt>transcriptional start site<\/dt>\n<dd>\n<p>site at which transcription begins<\/p>\n<\/dd>\n<dt>trp operon<\/dt>\n<dd>\n<p>series of genes necessary to synthesize tryptophan in prokaryotic cells<\/p>\n<\/dd>\n<dt>tryptophan<\/dt>\n<dd>\n<p>amino acid that can be synthesized by prokaryotic cells when necessary<\/p>\n<\/dd>\n<dt>untranslated region<\/dt>\n<dd>\n<p>segment of the RNA molecule that are not translated into protein. These regions lie before (upstream or 5&#8242;) and after (downstream or 3&#8242;) the protein-coding region<\/p>\n<\/dd>\n<\/dl>\n<\/div>\n<p>&lt;!&#8211;CNX: Start Area: &#8220;Sections Summary&#8221;&#8211;&gt;<\/p>\n<div class=\"cnx-eoc summary\">\n<div class=\"title\"><span>Sections Summary<\/span><\/div>\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<p><span id=\"m44534-fs-id1899262\"> <\/span>While all somatic cells within an organism contain the same DNA, not all cells within that organism express the same proteins. Prokaryotic organisms express the entire DNA they encode in every cell, but not necessarily all at the same time. Proteins are expressed only when they are needed. Eukaryotic organisms express a subset of the DNA that is encoded in any given cell. In each cell type, the type and amount of protein is regulated by controlling gene expression. To express a protein, the DNA is first transcribed into RNA, which is then translated into proteins. In prokaryotic cells, these processes occur almost simultaneously. In eukaryotic cells, transcription occurs in the nucleus and is separate from the translation that occurs in the cytoplasm. Gene expression in prokaryotes is regulated only at the transcriptional level, whereas in eukaryotic cells, gene expression is regulated at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels.<\/p>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<p><span id=\"m44535-fs-idm214780208\"> <\/span>The regulation of gene expression in prokaryotic cells occurs at the transcriptional level. There are three ways to control the transcription of an operon: repressive control, activator control, and inducible control. Repressive control, typified by the<span class=\"emphasis\"><em> trp<\/em><\/span> operon, uses proteins bound to the operator sequence to physically prevent the binding of RNA polymerase and the activation of transcription. Therefore, if tryptophan is not needed, the repressor is bound to the operator and transcription remains off. Activator control, typified by the action of CAP, increases the binding ability of RNA polymerase to the promoter when CAP is bound. In this case, low levels of glucose result in the binding of cAMP to CAP. CAP then binds the promoter, which allows RNA polymerase to bind to the promoter better. In the last example\u2014the <span class=\"emphasis\"><em>lac<\/em><\/span> operon\u2014two conditions must be met to initiate transcription. Glucose must not be present, and lactose must be available for the <span class=\"emphasis\"><em>lac<\/em><\/span> operon to be transcribed. If glucose is absent, CAP binds to the operator. If lactose is present, the repressor protein does not bind to its operator. Only when both conditions are met will RNA polymerase bind to the promoter to induce transcription.<\/p>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<p><span id=\"m44536-fs-id2682880\"> <\/span>In eukaryotic cells, the first stage of gene expression control occurs at the epigenetic level. Epigenetic mechanisms control access to the chromosomal region to allow genes to be turned on or off. These mechanisms control how DNA is packed into the nucleus by regulating how tightly the DNA is wound around histone proteins. The addition or removal of chemical modifications (or flags) to histone proteins or DNA signals to the cell to open or close a chromosomal region. Therefore, eukaryotic cells can control whether a gene is expressed by controlling accessibility to transcription factors and the binding of RNA polymerase to initiate transcription.<\/p>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<p><span id=\"m44538-fs-id2155116\"> <\/span>To start transcription, general transcription factors, such as TFIID, TFIIH, and others, must first bind to the TATA box and recruit RNA polymerase to that location. The binding of additional regulatory transcription factors to <span class=\"emphasis\"><em>cis<\/em><\/span>-acting elements will either increase or prevent transcription. In addition to promoter sequences, enhancer regions help augment transcription. Enhancers can be upstream, downstream, within a gene itself, or on other chromosomes. Transcription factors bind to enhancer regions to increase or prevent transcription.<\/p>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<p><span id=\"m44539-fs-id2572217\"> <\/span>Post-transcriptional control can occur at any stage after transcription, including RNA splicing, nuclear shuttling, and RNA stability. Once RNA is transcribed, it must be processed to create a mature RNA that is ready to be translated. This involves the removal of introns that do not code for protein. Spliceosomes bind to the signals that mark the exon\/intron border to remove the introns and ligate the exons together. Once this occurs, the RNA is mature and can be translated. RNA is created and spliced in the nucleus, but needs to be transported to the cytoplasm to be translated. RNA is transported to the cytoplasm through the nuclear pore complex. Once the RNA is in the cytoplasm, the length of time it resides there before being degraded, called RNA stability, can also be altered to control the overall amount of protein that is synthesized. The RNA stability can be increased, leading to longer residency time in the cytoplasm, or decreased, leading to shortened time and less protein synthesis. RNA stability is controlled by RNA-binding proteins (RPBs) and microRNAs (miRNAs). These RPBs and miRNAs bind to the 5&#8242; UTR or the 3&#8242; UTR of the RNA to increase or decrease RNA stability. Depending on the RBP, the stability can be increased or decreased significantly; however, miRNAs always decrease stability and promote decay.<\/p>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<p><span id=\"m44542-fs-id1511868\"> <\/span>Changing the status of the RNA or the protein itself can affect the amount of protein, the function of the protein, or how long it is found in the cell. To translate the protein, a protein initiator complex must assemble on the RNA. Modifications (such as phosphorylation) of proteins in this complex can prevent proper translation from occurring. Once a protein has been synthesized, it can be modified (phosphorylated, acetylated, methylated, or ubiquitinated). These post-translational modifications can greatly impact the stability, degradation, or function of the protein.<\/p>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<p><span id=\"m44548-fs-id3321766\"> <\/span>Cancer can be described as a disease of altered gene expression. Changes at every level of eukaryotic gene expression can be detected in some form of cancer at some point in time. In order to understand how changes to gene expression can cause cancer, it is critical to understand how each stage of gene regulation works in normal cells. By understanding the mechanisms of control in normal, non-diseased cells, it will be easier for scientists to understand what goes wrong in disease states including complex ones like cancer.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<p>&lt;!&#8211;CNX: Start Area: &#8220;Art Connections&#8221;&#8211;&gt;<\/p>\n<div class=\"cnx-eoc art-exercise\">\n<div class=\"title\"><span>Art Connections<\/span><\/div>\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44535-fs-idm113244368\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm111796848\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">5.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44535-fs-idm147603472\"> <\/span>    <\/p>\n<p><span id=\"m44535-fs-idm144508512\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xa0;16.5.&#xa0;\">Figure\u00a016.5<\/a> In <span class=\"emphasis\"><em>E. coli<\/em><\/span>, the <span class=\"emphasis\"><em>trp<\/em><\/span> operon is on by default, while the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is off. Why do you think that this is the case?<\/p>\n<\/p><\/div>\n<div id=\"m44535-fs-idm111796848\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm113244368\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44535-fs-idm18140960\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xa0;16.5.&#xa0;\">Figure\u00a016.5<\/a> Tryptophan is an amino acid essential for making proteins, so the cell always needs to have some on hand. However, if plenty of tryptophan is present, it is wasteful to make more, and the expression of the <span class=\"emphasis\"><em>trp<\/em><\/span> receptor is repressed. Lactose, a sugar found in milk, is not always available. It makes no sense to make the enzymes necessary to digest an energy source that is not available, so the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is only turned on when lactose is present.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44536-fs-id2134312\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id2596342\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">10.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44536-fs-id2138308\"> <\/span>    <\/p>\n<p><span id=\"m44536-fs-id1260103\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xa0;16.7.&#xa0;\">Figure\u00a016.7<\/a> In females, one of the two X chromosomes is inactivated during embryonic development because of epigenetic changes to the chromatin. What impact do you think these changes would have on nucleosome packing?<\/p>\n<\/div>\n<div id=\"m44536-fs-id2596342\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44536-fs-id2936478\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xa0;16.7.&#xa0;\">Figure\u00a016.7<\/a> The nucleosomes would pack more tightly together.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44542-fs-id2339974\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id1444395\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">22.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44542-fs-id2138282\"> <\/span><\/p>\n<p><span id=\"m44542-fs-id1974790\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xa0;16.13.&#xa0;\">Figure\u00a016.13<\/a> An increase in phosphorylation levels of eIF-2 has been observed in patients with neurodegenerative diseases such as Alzheimer\u2019s, Parkinson\u2019s, and Huntington\u2019s. What impact do you think this might have on protein synthesis?<\/p>\n<\/div>\n<div id=\"m44542-fs-id1444395\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id2339974\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44542-fs-id2137736\"> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xa0;16.13.&#xa0;\">Figure\u00a016.13<\/a> Protein synthesis would be inhibited.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">&lt;!&#8211;CNX: Start Area: &#8220;Multiple Choice&#8221;&#8211;&gt;<\/p>\n<div class=\"cnx-eoc multiple-choice\">\n<div class=\"title\"><span>Multiple Choice<\/span><\/div>\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44534-fs-id2187777\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id2745786\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">1.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44534-fs-id2689302\"> <\/span><\/p>\n<p><span id=\"m44534-fs-id2162541\"> <\/span>Control of gene expression in eukaryotic cells occurs at which level(s)?<\/p>\n<div class=\"orderedlist\"><span id=\"m44534-fs-id1731340\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>only the transcriptional level<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>epigenetic and transcriptional levels<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>epigenetic, transcriptional, and translational levels<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44534-fs-id2745786\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2187777\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44534-fs-id2726499\"> <\/span>D<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44534-fs-id1472236\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id2956599\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">2.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44534-fs-id1912048\"> <\/span><\/p>\n<p><span id=\"m44534-fs-id3456527\"> <\/span>Post-translational control refers to:<\/p>\n<div class=\"orderedlist\"><span id=\"m44534-fs-id3274389\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>regulation of gene expression after transcription<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>regulation of gene expression after translation<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>control of epigenetic activation<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>period between transcription and translation<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44534-fs-id2956599\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1472236\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44534-fs-id1511015\"> <\/span>B<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44535-fs-idm153813744\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm213368672\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">6.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44535-fs-idm88665920\"> <\/span><\/p>\n<p><span id=\"m44535-fs-idm164517008\"> <\/span>If glucose is absent, but so is lactose, the <span class=\"emphasis\"><em>lac<\/em><\/span> operon will be ________.<\/p>\n<div class=\"orderedlist\"><span id=\"m44535-fs-idm120554128\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>activated<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>repressed<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>activated, but only partially<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>mutated<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44535-fs-idm213368672\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm153813744\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44535-fs-idm70446512\"> <\/span>B<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44535-fs-idm98160192\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm101679744\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">7.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44535-fs-idm75160576\"> <\/span><\/p>\n<p><span id=\"m44535-fs-idm203465040\"> <\/span>Prokaryotic cells lack a nucleus. Therefore, the genes in prokaryotic cells are:<\/p>\n<div class=\"orderedlist\"><span id=\"m44535-fs-idm150743696\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>all expressed, all of the time<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>transcribed and translated almost simultaneously<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>transcriptionally controlled because translation begins before transcription ends<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>b and c are both true<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44535-fs-idm101679744\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm98160192\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44535-fs-idm226775584\"> <\/span>D<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44536-fs-id3112360\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id1426316\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">11.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44536-fs-id1426330\"> <\/span><\/p>\n<p><span id=\"m44536-fs-id2075390\"> <\/span>What are epigenetic modifications?<\/p>\n<div class=\"orderedlist\"><span id=\"m44536-fs-id2745125\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>the addition of reversible changes to histone proteins and DNA<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>the removal of nucleosomes from the DNA<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>the addition of more nucleosomes to the DNA<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>mutation of the DNA sequence<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44536-fs-id1426316\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id3112360\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44536-fs-id1595223\"> <\/span>A<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44536-fs-id2072168\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id2188544\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">12.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44536-fs-id1712063\"> <\/span><\/p>\n<p><span id=\"m44536-fs-id1912048\"> <\/span>Which of the following are true of epigenetic changes?<\/p>\n<div class=\"orderedlist\"><span id=\"m44536-fs-id1723647\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>allow DNA to be transcribed<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>move histones to open or close a chromosomal region<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>are temporary<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>all of the above<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44536-fs-id2188544\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2072168\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44536-fs-id1843643\"> <\/span>D<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44538-fs-id1808039\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id1962149\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">14.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44538-fs-id1723647\"> <\/span><\/p>\n<p><span id=\"m44538-fs-id1260103\"> <\/span>The binding of ________ is required for transcription to start.<\/p>\n<div class=\"orderedlist\"><span id=\"m44538-fs-id1912269\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>a protein<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>DNA polymerase<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>RNA polymerase<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>a transcription factor<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44538-fs-id1962149\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1808039\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44538-fs-id1627110\"> <\/span>C<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44538-fs-id1394736\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id2595874\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">15.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44538-fs-id1309467\"> <\/span><\/p>\n<p><span id=\"m44538-fs-id1594018\"> <\/span>What will result from the binding of a transcription factor to an enhancer region?<\/p>\n<div class=\"orderedlist\"><span id=\"m44538-fs-id2196025\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>decreased transcription of an adjacent gene<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>increased transcription of a distant gene<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>alteration of the translation of an adjacent gene<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>initiation of the recruitment of RNA polymerase<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44538-fs-id2595874\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1394736\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44538-fs-id2385867\"> <\/span>B<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44539-fs-id2685625\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id1684950\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">18.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44539-fs-id1876100\"> <\/span><\/p>\n<p><span id=\"m44539-fs-id1968588\"> <\/span>Which of the following are involved in post-transcriptional control?<\/p>\n<div class=\"orderedlist\"><span id=\"m44539-fs-id2642499\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>control of RNA splicing<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>control of RNA shuttling<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>control of RNA stability<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>all of the above<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44539-fs-id1684950\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2685625\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44539-fs-id2585833\"> <\/span>D<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44539-fs-id685962\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id2338011\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">19.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44539-fs-id2216370\"> <\/span><\/p>\n<p><span id=\"m44539-fs-id2914078\"> <\/span>Binding of an RNA binding protein will ________ the stability of the RNA molecule.<\/p>\n<div class=\"orderedlist\"><span id=\"m44539-fs-id1793945\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>increase<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>decrease<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>neither increase nor decrease<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>either increase or decrease<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44539-fs-id2338011\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id685962\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44539-fs-id1426330\"> <\/span>D<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44542-fs-id1404412\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id1670772\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">23.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44542-fs-id1651216\"> <\/span><\/p>\n<p><span id=\"m44542-fs-id1957056\"> <\/span>Post-translational modifications of proteins can affect which of the following?<\/p>\n<div class=\"orderedlist\"><span id=\"m44542-fs-id1442980\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>protein function<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>transcriptional regulation<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>chromatin modification<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>all of the above<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44542-fs-id1670772\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1404412\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44542-fs-id2682995\"> <\/span>A<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44548-fs-id1674486\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id1361234\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">27.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44548-fs-id1424266\"> <\/span><\/p>\n<p><span id=\"m44548-fs-id1964461\"> <\/span>Cancer causing genes are called ________.<\/p>\n<div class=\"orderedlist\"><span id=\"m44548-fs-id1719205\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>transformation genes<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>tumor suppressor genes<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>oncogenes<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>mutated genes<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44548-fs-id1361234\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id1674486\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44548-fs-id1457647\"> <\/span>C<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44548-fs-id2626129\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id2570415\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">28.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44548-fs-id2022725\"> <\/span><\/p>\n<p><span id=\"m44548-fs-id2348084\"> <\/span>Targeted therapies are used in patients with a set gene expression pattern. A targeted therapy that prevents the activation of the estrogen receptor in breast cancer would be beneficial to which type of patient?<\/p>\n<div class=\"orderedlist\"><span id=\"m44548-fs-id2385448\"> <\/span><\/p>\n<ol class=\"orderedlist\" type=\"a\">\n<li class=\"listitem\">\n<p>patients who express the EGFR receptor in normal cells<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>patients with a mutation that inactivates the estrogen receptor<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>patients with lots of the estrogen receptor expressed in their tumor<\/p>\n<\/li>\n<li class=\"listitem\">\n<p>patients that have no estrogen receptor expressed in their tumor<\/p>\n<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div id=\"m44548-fs-id2570415\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2626129\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44548-fs-id2169285\"> <\/span>C<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<p>&lt;!&#8211;CNX: Start Area: &#8220;Free Response&#8221;&#8211;&gt;<\/p>\n<div class=\"cnx-eoc free-response\">\n<div class=\"title\"><span>Free Response<\/span><\/div>\n<div class=\"section empty\">\n<div class=\"title\"><a href=\"#m44533\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Introduction<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44534\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.1<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Regulation of Gene Expression<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44534-fs-id2475955\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id1569019\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">3.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44534-fs-id2918717\"> <\/span><\/p>\n<p><span id=\"m44534-fs-id1310287\"> <\/span>Name two differences between prokaryotic and eukaryotic cells and how these differences benefit multicellular organisms.<\/p>\n<\/div>\n<div id=\"m44534-fs-id1569019\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2475955\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44534-fs-id1485528\"> <\/span>Eukaryotic cells have a nucleus, whereas prokaryotic cells do not. In eukaryotic cells, DNA is confined within the nuclear region. Because of this, transcription and translation are physically separated. This creates a more complex mechanism for the control of gene expression that benefits multicellular organisms because it compartmentalizes gene regulation.<\/p>\n<p><span id=\"m44534-eip-idp46390576\"> <\/span>Gene expression occurs at many stages in eukaryotic cells, whereas in prokaryotic cells, control of gene expression only occurs at the transcriptional level. This allows for greater control of gene expression in eukaryotes and more complex systems to be developed. Because of this, different cell types can arise in an individual organism.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44534-fs-id1443560\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44534-fs-id2126300\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">4.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44534-fs-id1442893\"> <\/span><\/p>\n<p><span id=\"m44534-fs-id2310144\"> <\/span>Describe how controlling gene expression will alter the overall protein levels in the cell.<\/p>\n<\/div>\n<div id=\"m44534-fs-id2126300\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1443560\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44534-fs-id2914874\"> <\/span>The cell controls which proteins are expressed and to what level each protein is expressed in the cell. Prokaryotic cells alter the transcription rate to turn genes on or off. This method will increase or decrease protein levels in response to what is needed by the cell. Eukaryotic cells change the accessibility (epigenetic), transcription, or translation of a gene. This will alter the amount of RNA and the lifespan of the RNA to alter the amount of protein that exists. Eukaryotic cells also control protein translation to increase or decrease the overall levels. Eukaryotic organisms are much more complex and can manipulate protein levels by changing many stages in the process.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44535\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.2<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Prokaryotic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44535-fs-idm269564080\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm101659264\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">8.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44535-fs-idm224823216\"> <\/span><\/p>\n<p><span id=\"m44535-fs-idm152304928\"> <\/span>Describe how transcription in prokaryotic cells can be altered by external stimulation such as excess lactose in the environment.<\/p>\n<\/div>\n<div id=\"m44535-fs-idm101659264\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm269564080\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44535-fs-idm106482176\"> <\/span>Environmental stimuli can increase or induce transcription in prokaryotic cells. In this example, lactose in the environment will induce the transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon, but only if glucose is not available in the environment.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44535-fs-idm20214992\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44535-fs-idm214699984\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">9.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44535-fs-idm103662208\"> <\/span><\/p>\n<p><span id=\"m44535-fs-idm159081360\"> <\/span>What is the difference between a repressible and an inducible operon?<\/p>\n<\/div>\n<div id=\"m44535-fs-idm214699984\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm20214992\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44535-fs-idm202138176\"> <\/span>A repressible operon uses a protein bound to the promoter region of a gene to keep the gene repressed or silent. This repressor must be actively removed in order to transcribe the gene. An inducible operon is either activated or repressed depending on the needs of the cell and what is available in the local environment.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44536\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.3<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Epigenetic Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44536-fs-id1876408\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44536-fs-id2025774\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">13.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44536-fs-id1318470\"> <\/span><\/p>\n<p><span id=\"m44536-fs-id2009095\"> <\/span>In cancer cells, alteration to epigenetic modifications turns off genes that are normally expressed. Hypothetically, how could you reverse this process to turn these genes back on?<\/p>\n<\/div>\n<div id=\"m44536-fs-id2025774\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id1876408\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44536-fs-id2051513\"> <\/span>You can create medications that reverse the epigenetic processes (to add histone acetylation marks or to remove DNA methylation) and create an open chromosomal configuration.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44538\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.4<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Transcription Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44538-fs-id1942060\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id2317344\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">16.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44538-fs-id2573671\"> <\/span><\/p>\n<p><span id=\"m44538-fs-id2570388\"> <\/span>A mutation within the promoter region can alter transcription of a gene. Describe how this can happen.<\/p>\n<\/div>\n<div id=\"m44538-fs-id2317344\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1942060\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44538-fs-id2269310\"> <\/span>A mutation in the promoter region can change the binding site for a transcription factor that normally binds to increase transcription. The mutation could either decrease the ability of the transcription factor to bind, thereby decreasing transcription, or it can increase the ability of the transcription factor to bind, thus increasing transcription.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44538-fs-id2025518\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44538-fs-id2169012\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">17.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44538-fs-id2574201\"> <\/span><\/p>\n<p><span id=\"m44538-fs-id2272706\"> <\/span>What could happen if a cell had too much of an activating transcription factor present?<\/p>\n<\/div>\n<div id=\"m44538-fs-id2169012\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id2025518\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44538-fs-id2239602\"> <\/span>If too much of an activating transcription factor were present, then transcription would be increased in the cell. This could lead to dramatic alterations in cell function.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44539\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.5<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Post-transcriptional Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44539-fs-id1511123\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id2714180\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">20.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44539-fs-id2315152\"> <\/span><\/p>\n<p><span id=\"m44539-fs-id2118982\"> <\/span>Describe how RBPs can prevent miRNAs from degrading an RNA molecule.<\/p>\n<\/div>\n<div id=\"m44539-fs-id2714180\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id1511123\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44539-fs-id3327891\"> <\/span>RNA binding proteins (RBP) bind to the RNA and can either increase or decrease the stability of the RNA. If they increase the stability of the RNA molecule, the RNA will remain intact in the cell for a longer period of time than normal. Since both RBPs and miRNAs bind to the RNA molecule, RBP can potentially bind first to the RNA and prevent the binding of the miRNA that will degrade it.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44539-fs-id2134312\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44539-fs-id1876054\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">21.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44539-fs-id2984456\"> <\/span><\/p>\n<p><span id=\"m44539-fs-id1808039\"> <\/span>How can external stimuli alter post-transcriptional control of gene expression?<\/p>\n<\/div>\n<div id=\"m44539-fs-id1876054\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44539-fs-id1894654\"> <\/span>External stimuli can modify RNA-binding proteins (i.e., through phosphorylation of proteins) to alter their activity.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44542\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.6<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Eukaryotic Translational and Post-translational Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44542-fs-id1650941\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id2733341\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">24.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44542-fs-id1867175\"> <\/span><\/p>\n<p><span id=\"m44542-fs-id3327918\"> <\/span>Protein modification can alter gene expression in many ways. Describe how phosphorylation of proteins can alter gene expression.<\/p>\n<\/div>\n<div id=\"m44542-fs-id2733341\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1650941\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44542-fs-id2638006\"> <\/span>Because proteins are involved in every stage of gene regulation, phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering the transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44542-fs-id1680861\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id2098858\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">25.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44542-fs-id2911418\"> <\/span><\/p>\n<p><span id=\"m44542-fs-id2062329\"> <\/span>Alternative forms of a protein can be beneficial or harmful to a cell. What do you think would happen if too much of an alternative protein bound to the 3&#8242; UTR of an RNA and caused it to degrade?<\/p>\n<\/div>\n<div id=\"m44542-fs-id2098858\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1680861\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44542-fs-id2874182\"> <\/span>If the RNA degraded, then less of the protein that the RNA encodes would be translated. This could have dramatic implications for the cell.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44542-fs-id1259369\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44542-fs-id1364111\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">26.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44542-fs-id1771623\"> <\/span><\/p>\n<p><span id=\"m44542-fs-id1511201\"> <\/span>Changes in epigenetic modifications alter the accessibility and transcription of DNA. Describe how environmental stimuli, such as ultraviolet light exposure, could modify gene expression.<\/p>\n<\/div>\n<div id=\"m44542-fs-id1364111\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1259369\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44542-fs-id1353371\"> <\/span>Environmental stimuli, like ultraviolet light exposure, can alter the modifications to the histone proteins or DNA. Such stimuli may change an actively transcribed gene into a silenced gene by removing acetyl groups from histone proteins or by adding methyl groups to DNA.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"section\">\n<div class=\"title\"><a href=\"#m44548\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-n\">16.7<\/span><span class=\"cnx-gentext-section cnx-gentext-autogenerated\">.\u00a0<\/span><span class=\"cnx-gentext-section cnx-gentext-t\">Cancer and Gene Regulation<\/span><\/span><\/a><\/div>\n<div class=\"body\">\n<div id=\"m44548-fs-id2020932\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id2080482\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">29.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44548-fs-id1354125\"> <\/span><\/p>\n<p><span id=\"m44548-fs-id2167622\"> <\/span>New drugs are being developed that decrease DNA methylation and prevent the removal of acetyl groups from histone proteins. Explain how these drugs could affect gene expression to help kill tumor cells.<\/p>\n<\/div>\n<div id=\"m44548-fs-id2080482\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2020932\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44548-fs-id2689865\"> <\/span>These drugs will keep the histone proteins and the DNA methylation patterns in the open chromosomal configuration so that transcription is feasible. If a gene is silenced, these drugs could reverse the epigenetic configuration to re-express the gene.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"m44548-fs-id2048357\" class=\"exercise\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><a class=\"solution-number\" href=\"#m44548-fs-id2935760\"><span class=\"cnx-gentext-exercise cnx-gentext-autogenerated\">Exercise <\/span><span class=\"cnx-gentext-exercise cnx-gentext-n\">30.<\/span><\/a><\/span><\/div>\n<div class=\"body\">&lt;!&#8211;calling informal.object&#8211;&gt;<\/p>\n<div class=\"problem\"><span id=\"m44548-fs-id2319451\"> <\/span><\/p>\n<p><span id=\"m44548-fs-id2057320\"> <\/span>How can understanding the gene expression pattern in a cancer cell tell you something about that specific form of cancer?<\/p>\n<\/div>\n<div id=\"m44548-fs-id2935760\" class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2048357\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span id=\"m44548-fs-id2660635\"> <\/span>Understanding which genes are expressed in a cancer cell can help diagnose the specific form of cancer. It can also help identify treatment options for that patient. For example, if a breast cancer tumor expresses the EGFR in high numbers, it might respond to specific anti-EGFR therapy. If that receptor is not expressed, it would not respond to that therapy.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"cnx-eoc cnx-solutions\">\n<div class=\"title\">Solutions<\/div>\n<p>&lt;!&#8211;CNX: Start Area: &#8220;Art Connections&#8221;&#8211;&gt;<\/p>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm113244368\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44535-fig-ch16_02_03\" title=\"Figure&#xa0;16.5.&#xa0;\">Figure\u00a016.5<\/a> Tryptophan is an amino acid essential for making proteins, so the cell always needs to have some on hand. However, if plenty of tryptophan is present, it is wasteful to make more, and the expression of the <span class=\"emphasis\"><em>trp<\/em><\/span> receptor is repressed. Lactose, a sugar found in milk, is not always available. It makes no sense to make the enzymes necessary to digest an energy source that is not available, so the <span class=\"emphasis\"><em>lac<\/em><\/span> operon is only turned on when lactose is present.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44536-fig-ch16_03_02\" title=\"Figure&#xa0;16.7.&#xa0;\">Figure\u00a016.7<\/a> The nucleosomes would pack more tightly together.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id2339974\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span><a class=\"xref target-figure\" href=\"ch16.html#m44542-fig-ch16_06_01\" title=\"Figure&#xa0;16.13.&#xa0;\">Figure\u00a016.13<\/a> Protein synthesis would be inhibited.<\/p>\n<\/div>\n<\/div>\n<p>&lt;!&#8211;CNX: Start Area: &#8220;Multiple Choice&#8221;&#8211;&gt;<\/p>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2187777\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>D<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1472236\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>B<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm153813744\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>B<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm98160192\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>D<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id3112360\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>A<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id2072168\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>D<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1808039\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>C<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1394736\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>B<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2685625\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>D<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id685962\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>D<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1404412\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>A<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id1674486\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>C<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2626129\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>C<\/p>\n<\/div>\n<\/div>\n<p>&lt;!&#8211;CNX: Start Area: &#8220;Free Response&#8221;&#8211;&gt;<\/p>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id2475955\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>Eukaryotic cells have a nucleus, whereas prokaryotic cells do not. In eukaryotic cells, DNA is confined within the nuclear region. Because of this, transcription and translation are physically separated. This creates a more complex mechanism for the control of gene expression that benefits multicellular organisms because it compartmentalizes gene regulation.<\/p>\n<p><span> <\/span>Gene expression occurs at many stages in eukaryotic cells, whereas in prokaryotic cells, control of gene expression only occurs at the transcriptional level. This allows for greater control of gene expression in eukaryotes and more complex systems to be developed. Because of this, different cell types can arise in an individual organism.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44534-fs-id1443560\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>The cell controls which proteins are expressed and to what level each protein is expressed in the cell. Prokaryotic cells alter the transcription rate to turn genes on or off. This method will increase or decrease protein levels in response to what is needed by the cell. Eukaryotic cells change the accessibility (epigenetic), transcription, or translation of a gene. This will alter the amount of RNA and the lifespan of the RNA to alter the amount of protein that exists. Eukaryotic cells also control protein translation to increase or decrease the overall levels. Eukaryotic organisms are much more complex and can manipulate protein levels by changing many stages in the process.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm269564080\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>Environmental stimuli can increase or induce transcription in prokaryotic cells. In this example, lactose in the environment will induce the transcription of the <span class=\"emphasis\"><em>lac<\/em><\/span> operon, but only if glucose is not available in the environment.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44535-fs-idm20214992\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>A repressible operon uses a protein bound to the promoter region of a gene to keep the gene repressed or silent. This repressor must be actively removed in order to transcribe the gene. An inducible operon is either activated or repressed depending on the needs of the cell and what is available in the local environment.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44536-fs-id1876408\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>You can create medications that reverse the epigenetic processes (to add histone acetylation marks or to remove DNA methylation) and create an open chromosomal configuration.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id1942060\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>A mutation in the promoter region can change the binding site for a transcription factor that normally binds to increase transcription. The mutation could either decrease the ability of the transcription factor to bind, thereby decreasing transcription, or it can increase the ability of the transcription factor to bind, thus increasing transcription.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44538-fs-id2025518\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>If too much of an activating transcription factor were present, then transcription would be increased in the cell. This could lead to dramatic alterations in cell function.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id1511123\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>RNA binding proteins (RBP) bind to the RNA and can either increase or decrease the stability of the RNA. If they increase the stability of the RNA molecule, the RNA will remain intact in the cell for a longer period of time than normal. Since both RBPs and miRNAs bind to the RNA molecule, RBP can potentially bind first to the RNA and prevent the binding of the miRNA that will degrade it.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44539-fs-id2134312\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>External stimuli can modify RNA-binding proteins (i.e., through phosphorylation of proteins) to alter their activity.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1650941\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>Because proteins are involved in every stage of gene regulation, phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering the transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1680861\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>If the RNA degraded, then less of the protein that the RNA encodes would be translated. This could have dramatic implications for the cell.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44542-fs-id1259369\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>Environmental stimuli, like ultraviolet light exposure, can alter the modifications to the histone proteins or DNA. Such stimuli may change an actively transcribed gene into a silenced gene by removing acetyl groups from histone proteins or by adding methyl groups to DNA.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2020932\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>These drugs will keep the histone proteins and the DNA methylation patterns in the open chromosomal configuration so that transcription is feasible. If a gene is silenced, these drugs could reverse the epigenetic configuration to re-express the gene.<\/p>\n<\/div>\n<\/div>\n<div class=\"solution labeled\">&lt;!&#8211;calling formal.object&#8211;&gt;<\/p>\n<div class=\"title\"><span><span class=\"epub-only pre-text\"> (<\/span><a class=\"solution\" href=\"ch16.html#m44548-fs-id2048357\">Return to Exercise<\/a><span class=\"epub-only post-text\">)<\/span><\/span><\/div>\n<div class=\"body\">\n<p><span> <\/span>Understanding which genes are expressed in a cancer cell can help diagnose the specific form of cancer. It can also help identify treatment options for that patient. For example, if a breast cancer tumor expresses the EGFR in high numbers, it might respond to specific anti-EGFR therapy. If that receptor is not expressed, it would not respond to that therapy.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"author":17,"menu_order":18,"template":"","meta":{"_candela_citation":"[]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-520","chapter","type-chapter","status-publish","hentry"],"part":21,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/520","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/users\/17"}],"version-history":[{"count":1,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/520\/revisions"}],"predecessor-version":[{"id":522,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/520\/revisions\/522"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/parts\/21"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapters\/520\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/media?parent=520"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/pressbooks\/v2\/chapter-type?post=520"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/contributor?post=520"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/umd-publichealthbio\/wp-json\/wp\/v2\/license?post=520"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}