10.82 Epigenetics

What is epigenetics? Epigenetics means “above the genome.” The nucleotide sequence of the human genome is known, and there is surprisingly little difference between individuals. However, the 2 main epigenetic modifications play a major role in determining what genes are expressed:

DNA methylation

Histone modification

These epigenetic modifications are illustrated in the following link.

Web Link

Epigenetic modifications

DNA methylation is the addition of a methyl group to a DNA base, which decreases gene transcription. Conversely, demethylation increases gene transcription.

DNA does not exist simply as long strands of double helix, instead it is packaged and shaped so that it can fit in the nucleus of our cells. The first part of this packaging is that DNA is wrapped around proteins called histones as shown below.

Figure 10.821 DNA is wrapped around histones1

Histone modification occurs when there are additions or subtractions to the histones themselves. The most common is acetylation (addition of an acetyl group) or deacetylation of histones. The structure of acetyl is shown below.

Figure 10.822 Structure of acetyl2

Histone acetylation causes the DNA structure to open up so that transcription can occur. Histone deacetylation causes the DNA to become more tightly packed, preventing transcription from occurring.

Together, these modifications to DNA and histones are known as the epigenetic code. The following two videos do a good job explaining epigenetics and tying together its two different methods of modification:

Web Links

Video: A Tale of Two Mice (4:39)

Video: Histone Modifications (2:18)

How does this relate to biotin? Histones can be biotinylated, or have biotin added to the histone. However, it should be noted that histone biotinylation is rare (<0.001% of human histones H3 and H4), so it is questionable how much impact this action has3.

References & Links

1. http://en.wikipedia.org/wiki/File:Nucleosome_structure.png
2. http://en.wikipedia.org/wiki/File:Acetyl.svg

3. Kuroshi T, Rios-Avila L, Pestinger V, Wijeratne SSK, Zempleni J. (2011) Biotinylation is a natural, albeit rare, modification of human histones. Mol Genet Metab, 104, 537-545.

Links

Epigenetic modifications – http://www.nature.com/nature/journal/v441/n7090/images/441143a-i2.0.jpg

Videos

A Tale of Two Mice – https://www.youtube.com/watch?v=OOiCu5kzGxg
Histone Modifications – http://www.youtube.com/watch?v=eYrQ0EhVCYA