Gene regulation - An Introduction

Gene expression can be controlled at any of several stages, which we divide broadly into transcription, processing, and translation:

• Transcription often is controlled at the stage of initiation. Transcription is not usually controlled at elongation, but may be controlled at termination to determine whether RNA polymerase is allowed to proceed past a terminator to the gene(s) beyond.

• In eukaryotic cells, processing of the RNA product may be regulated at the stages of modification, splicing, transport, or stability. In bacteria, an mRNA is in principle available for translation as soon as (or even while) it is being synthesized, and these stages of control are not available.
• Translation may be regulated, usually at the stages of initiation and termination (like transcription). Regulation of initiation is formally analogous to the regulation of transcription: the circuitry can be drawn in similar terms for regulating initiation of transcription on DNA or initiation of translation on RNA.

The basic concept for how transcription is controlled in bacteria was provided by the classic formulation of the model for control of gene expression by Jacob and Monod in 1961 (Jacob and Monod, 1961). They distinguished between two types of sequences in DNA: sequences that code for trans-acting products; and cis-acting sequences that function exclusively within the DNA. Gene activity is regulated by the specific interactions of the trans-acting products (usually proteins) with the cis-acting sequences (usually sites in DNA). In more formal terms:

• A gene is a sequence of DNA that codes for a diffusible product. This product may be protein (as in the case of the majority of genes) or may be RNA (as in the case of genes that code for tRNA and rRNA). The crucial feature is that the product diffuses away from its site of synthesis to act elsewhere. Any gene product that is free to diffuse to find its target is described as trans-acting.
• The description cis-acting applies to any sequence of DNA that is not converted into any other form, but that functions exclusively as a DNA sequence in situ, affecting only the DNA to which it is physically linked. (In some cases, a cis-acting sequence functions in an RNA rather than in a DNA molecule.

To help distinguish between the components of regulatory circuits and the genes that they regulate, we sometimes use the terms structural gene and regulator gene. A structural gene is simply any gene that codes for a protein (or RNA) product. Structural genes represent an enormous variety of protein structures and functions, including structural proteins, enzymes with catalytic activities, and regulatory proteins. A regulator gene simply describes a gene that codes for a protein (or an RNA) involved in regulating the expression of other genes.

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Figure 10.1  
A regulator gene codes for a protein that acts at a target site on DNA.

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The simplest form of the regulatory model is illustrated in Figure above: a regulator gene codes for a protein that controls transcription by binding to particular site(s) on DNA. This interaction can regulate a target gene in either a positive manner (the interaction turns the gene on) or in a negative manner (the interaction turns the gene off). The sites on DNA are usually (but not exclusively) located just upstream of the target gene.