Topic_7 - Topic 7: Regulation of Gene Expression I...

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Unformatted text preview: Topic 7: Regulation of Gene Expression I Fundamentals of Microbiology (Biology 140) Course notes Dr. Josh D. Neufeld Learning Objectives: You should understand the concept of genetic regulation, the different levels at which this regulation may occur, and some of the specific mechanisms for gene regulation. The different strategies employed by synthetic vs. degradation pathways will be discussed. Interaction of proteins with specific sequences of DNA is crucial to regulation at the level of transcription. Enzymes and other proteins are not all required by the cell at the same time, under the same conditions. Some are required only under certain conditions, while others are required under other conditions. The cell responds by regulating the activity or amount of a given enzyme in relation to the requirements of the cell. There are many levels at which this regulation may occur (Figure 9.1). The first level that we will look at is post ­ translational regulation. This is the level at which response may be the most rapid. In a pathway of many steps, the final product, the allosteric effector, often inhibits the activity of the enzyme at the first unique step of the pathway, resulting in shutdown of the pathway. The inhibitory product binds to the enzyme at the allosteric site (Figure 5.30), changing the conformation of the enzyme so that the substrate is unable to bind at the active site. In other cases, regulation might be due to covalent modification such as adenylation, phosphorylation or methylation. An example of regulation of enzyme activity by adenylation is shown in Figure 5.32. One of the most important levels of gene regulation is that of transcription. Regulation at this level ensures that enzymes are not synthesized unless the cell needs them. Transcription may be regulated by repression (Figure 9.5) or induction (Figure 9.6) by specific small molecules called effectors. Genes for the production of biosynthetic enzymes are often regulated by repression, and the effectors are usually products of the pathway, while genes for the production of catabolic enzymes are often regulated by induction, and the effectors are usually substrates. See Figures 9.7 and 9.8 for examples of mechanisms of repression and induction. Note that in both of these examples, effector molecules interact with allosteric repressor molecules to influence their binding of the operator region of the gene. Binding to the operator blocks the path of the RNA polymerase, thus inhibiting transcription. Both of these types of regulation involve repressors, and the term for this type of regulation is thus negative control. In some cases, transcription is mediated by an activator protein that operates by increasing the affinity of the RNA polymerase to the promoter (Figure 9.9). Effector molecules bind to the activator protein, which changes the conformation so that the activator protein can bind to the activator binding site on the DNA. This binding of the Fundamentals of Microbiology (Biology 140) Course notes Dr. Josh D. Neufeld activator protein to the DNA increases the affinity of the RNA polymerase to the promoter. This type of regulation is called positive control. An important characteristic of regulatory proteins that interact with DNA is their ability to bind DNA in a sequence ­specific manner. Many of these regulatory proteins are dimers, and interact with inverted repeats of DNA (Figure 9.2). The helix ­turn ­helix (Figure 9.3) is a structure that is commonly seen in DNA binding proteins. ...
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