Activators and Inducers

Learning Outcomes

  • Explain the role of activators and inducers in positive gene regulation

Catabolite Activator Protein (CAP): An Activator Regulator

Just as the trp operon is negatively regulated by tryptophan molecules, there are proteins that bind to the operator sequences that act as a positive regulator to turn genes on and activate them. For example, when glucose is scarce, E. coli bacteria can turn to other sugar sources for fuel. To do this, new genes to process these alternate sugars 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 E. coli. When glucose levels decline in the cell, accumulating cAMP binds to the positive regulator catabolite activator protein (CAP), 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 (Figure 1). 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.

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–cAMP complex binds to the promoter and increases RNA polymerase activity. As a result, the rate of RNA synthesis is increased.

Figure 1. When glucose levels fall, E. coli 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.

Lactose Operon: An Inducer Operon

The third type of gene regulation in prokaryotic cells occurs through inducible operons, which have proteins that bind to activate or repress transcription depending on the local environment and the needs of the cell. The lac operon is a typical inducible operon. As mentioned previously, E. coli is able to use other sugars as energy sources when glucose concentrations are low. One such sugar source is lactose. The lac operon encodes the genes necessary to acquire and process the lactose from the local environment. The Z gene of the lac operon encodes beta-galactosidase, which breaks lactose down to glucose and galactose.

However, for the lac 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 lac operon be transcribed (Figure 2). In the absence of glucose, the binding of the CAP protein makes transcription of the lac operon more effective. When lactose is present, its metabolite, allolactose, binds to the lac repressor and changes its shape so that it cannot bind to the lac operator to prevent transcription. This combination of conditions makes sense for the cell, because it would be energetically wasteful to synthesize the enzymes to process lactose if glucose was plentiful or lactose was not available. It should be mentioned that the lac operon is transcribed at a very low rate even when glucose is present and lactose absent.

Practice Question

Transcription of the lac 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.

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–CAP complex to the promoter stimulates RNA polymerase activity and increases RNA synthesis. However, even in the presence of the cAMP–CAP complex, RNA synthesis is blocked if the repressor binds to the promoter.

Figure 2. Regulation of the lac operon.

 

In E. coli, the trp operon is on by default, while the lac operon is off. Why do you think this is the case?

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 lac operon transcribed (Table 1).

Table 1. Signals that Induce or Repress Transcription of the lac Operon
Glucose CAP binds Lactose Repressor binds Transcription
+ − − + No
+ − + − Some
− + − + No
− + + − Yes

Watch an animated tutorial about the workings of lac operon here.

You can view the transcript for “Operon LAC” here (link opens in new window).

Practice Questions

If glucose is absent, but so is lactose, the lac operon will be ________.

  1. activated
  2. repressed
  3. activated, but only partially
  4. mutated

Describe how transcription in prokaryotic cells can be altered by external stimulation such as excess lactose in the environment.

What is the difference between a repressible and an inducible operon?

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