Most mechanisms of gene regulation in prokaryotes block or enhance the initiation of transcription. Later steps in gene expression are potential targets for fine-tuning the amount of gene products that accumulate in cells.
In the lac operon model proposed by Jacob and Monod, the binding of a repressor protein (encoded by the lacI gene) to the DNA operator prevents transcription of the structural genes lacZ, lacY, and lacA in the absence of the inducer lactose. When lactose is present, its binding to the repressor induces expression of the structural genes by causing the repressor to change its shape and lose its ability to bind to the operator.
A critical, general principle emerges from the lac operon studies: Regulatory genes usually encode trans-acting regulatory proteins that interact with cis-acting regulatory DNA elements located near the promoter (such as the operator). Negative regulatory proteins prevent or diminish the rate of transcription, while positive regulatory proteins enhance transcription.
Many types of coordinate gene regulation result from the clustering of genes into operons that are transcribed into a single polycistronic mRNA from a single promoter.
The binding of repressor proteins to operators can be influenced by either inducers (as for the lac repressor) or corepressors (as for the trp operon).
Catabolite repression regulates certain catabolite operons by preventing the CRP protein, a positive regulator, from binding to the operons' promoter region in the presence of high concentrations of glucose.
Many regulatory proteins, both positive and negative, contain a helix-turn-helix motif, function as oligomers that bind to more than one DNA site, and interact with RNA polymerase to prevent or assist its function.
Attenuation, a form of fine-tuning for operons involved in the biosynthesis of amino acids, is based on the amount of premature termination of mRNA transcription. The termination, in turn, is determined by the intracellular concentration of tRNAs charged with the amino acid produced by the enzyme products of the structural genes in the operon.
Cells can express different sets of genes at different times or under different conditions by using alternate sigma factors or by producing novel RNA polymerases that recognize different classes of promoters.
