Control of Gene Expression

Chapter title: Control of Gene Expression

Control of gene expression basically occurs at two levels, prior to transcription and post-transcriptionally. One can make a reasonable argument that post-transcriptional control of gene expression is not control at the level of the gene and such an argument would be reasonable. In this lecture, therefore, we will consider only those mechanisms which modify gene expression by either acting to increase the rate of transcription of individuals genes or, by contrast, inhibit the rate of transcription of individuals genes. Such mechanisms invariably involve the sensing of intracellular or extracellular conditions by proteins (see metabolic control) which then either bind to DNA, bind to, modify, or cause the modification of proteins which in turn bind to DNA, or which modify or cause the modification of other factors involved in transcription (such as RNA polymerase). Some of these transcritpion proteins interfere with RNA polymerase action (Repressors; negative control) while others enhance RNA polymerase action (activators). In this lecture we will consider both cases, and more.

Minimizing resources devoted to protein synthesis:

It can be wasteful, and sometimes even harmful, to express a gene at an inappropriate time.
Synthesizing proteins, for example, from transcription through translation and beyond, is metabolically expensive.
Consequently, regulation of protein action is both important and most economically achieved as early in protein synthesis as possible.

Transcriptional control is particularly economical:

Most economical is at a point prior to transcription since transcription is the first relatively expensive step in protein syntehsis.
Thus, the activity of specific proteins about cells is very often regulated through either blocks (negative control) on or enhancement (positive control) of RNA polymerase action and thus at the level of transcription.

The binding of a specific protein (repressor protein) to DNA at a point that interferes with the action of RNA polymerase on a specific gene is a form of negative control of protein synthesis.
This interference with RNA polymerase activity is termed repression (of the action of RNA polymerase) and the consequent to this lack of gene expression a gene is described as repressed.

Action results in lack of activity:

This form of control of gene expression is called negative control because the controlling action results in an absence of activity.
Contrast this with positive control.

Action results in activity:

In contrast to negative control, very often a specific gene requires the binding of a specific protein (an activating protein) in order to acheive RNA polymerase binding and gene expression.
This type of control of gene expression is termed activation since in its absence the gene is not active (i.e., is not expressed).

This type of control is also termed positive control in the sense that the action of the activating protein results in a positive action: gene expression.

Collectively repressor proteins and activator proteins are termed regulatory proteins.

Changes in protein shape:

regulatory proteins commonly act through allosteric means.
That is, a product of or substrate for a single enzyme or entire biochemical pathway may bind to a regulatory proteins, changing its shape so that it now either can bind to specific regions of DNA or can no longer bind to these same regions (thus allowing it to or preventing it from doing its regulatory action, respectively).

For example, the product of an enzyme may bind to a repressor protein thus turning off the expression of the particular protein when product is particularly abundant.
Alternatively, a substrate for a particular enzyme may bind a specific activator protein/A thus turning on the expression of the particular protein only when substrate is present for it to act upon.

RNA polymerase binding region:

A region of DNA found prior to the region of a gene which is copied to make mRNA (i.e., the region that is transcribed; I use the term prior to in the sense of the direction of travel of the RNA polymerase during the transcription process).
It is to the promotor that the RNA polymerase first binds.

Activators enhance RNA polymerase binding to promotors (i.e., they promote RNA polymerase binding).
Repressors, on the other hand, bind between the promotor and the region of the gene which is transcribed, thus interfering with RNA polymerase action (i.e., Repressors block transcription).

Many genes are expressed under all circumstances by a cell or organism, regardless of environmental influences (e.g., presence or absence of substrates and products, ect.).
That is, such proteins are not regulated in the sense as discussed above.
These genes are said to be constitutively expressed (that is, constantly).

Raven, P.H., Johnson, G.B. (1995). Biology (updated version). Third Edition. Wm. C. Brown publishers, Dubuque, Iowa. pp. 313-319.