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Modern Genetic Analysis Chapter 14. Regulation of Gene Transcription
The Basics of Prokaryotic Transcriptional Regulation

To understand how prokaryotic transcriptional regulation is accomplished, we shall consider a series of controlled sequence-specific DNAprotein interactions at DNA target sites located near the beginning of transcription of a gene. Two types of DNAprotein interactions are required for regulated transcription.

One required DNAprotein interaction determines where transcription begins. It involves the DNA segment called the promoter and the protein RNA polymerase. When RNA polymerase binds to the promoter DNA, transcription can initiate a few bases away from the promoter site. Every gene must have a promoter or it cannot be transcribed.

The other type of required DNAprotein interaction regulates whether or not promoter-driven transcription occurs. DNA segments near the promoter serve as protein-binding sitesmost of these sites are termed operatorsfor regulatory proteins called activators and repressors. For some genes, the binding of an activator protein to its target DNA site is a necessary prerequisite for transcription to begin. Such instances are sometimes referred to as positive regulation because it is the presence of the bound protein that is required for transcription (Figure 14-1). For other genes, preventing the binding of a repressor protein to its target site is a necessary prerequisite for transcription to begin. Such cases are sometimes termed negative regulation because it is the absence of the bound protein that allows transcription to occur. How do activators and repressors regulate transcription? Often, a DNA-bound activator protein acts at the level of transcription initiation, by physically helping to tether RNA polymerase to its nearby promoter. A DNA-bound repressor protein typically acts either by physically interfering with the binding of RNA polymerase to its promoter (blocking transcription initiation) or by impeding the movement of RNA polymerase along the DNA chain (blocking transcription elongation).

MESSAGE
Genes must contain two kinds of binding sites to permit regulated transcription. First, binding sites for RNA polymerase must be present. Second, binding sites for activator or repressor proteins must be present in the vicinity of the promoter.

For activator or repressor proteins to do their job, each must be able to exist in two states: one that can bind its DNA targets and one that cannot. The binding state must be in accord with the cellular environment; that is, be appropriate for a given set of physiological conditions. For many activator or repressor proteins, the way that DNA binding is regulated is through the interaction of two different sites in the three-dimensional structure of the protein. One site is the DNA-binding domain. The other site, the allosteric site, acts as the toggle switch that sets the DNA-binding domain in one of two modes: functional or nonfunctional. The allosteric site interacts with small molecules called allosteric effectors. In our earlier example of lactose metabolism, the metabolite lactose would be an allosteric effector. An allosteric effector binds to the allosteric site of the regulatory protein in such a way that it changes the structure of the DNA-binding domain. Some activator or repressor proteins must bind to their allosteric effectors to bind DNA. Others can bind DNA only in the absence of their allosteric effectors (Figure 14-2).

MESSAGE
Allosteric effectors work like toggle switches to control the ability of activator or repressor proteins to bind to their DNA target sites.

© 1999 by W. H. Freeman and Company. All rights reserved.