Gene regulation is often mediated by proteins that react to environmental signals by raising or lowering the transcription rates of specific genes. The logic of this regulation is straightforward. In order for regulation to operate appropriately, the regulatory proteins have built-in sensors that continually monitor cellular conditions. The activities of these proteins would then depend on the right set of environmental conditions.

In bacteria and their viruses, the control of several structural genes may be coordinated by clustering the genes together into operons on the chromosome so that they are transcribed into multigenic mRNAs. Coordinated control simplifies the task for bacteria because one cluster of regulatory sites per operon is sufficient to regulate the expression of all the operon’s genes. Alternatively, coordinate control can also be achieved through discrete σ factors that regulate dozens of independent promoters simultaneously.

In negative regulatory control, a repressor protein blocks transcription by binding to DNA at the operator site. Negative regulatory control is exemplified by the lac system. Negative regulation is one very straightforward way for the lac system to shut down genes in the absence of appropriate sugars in the environment. In positive regulatory control, protein factors are required to activate transcription. Some prokaryotic gene control, such as that for catabolite repression, operates through positive gene control.

Many regulatory proteins are members of families of proteins that have very similar DNA-binding motifs, such as the helix-turn-helix domain. Other parts of the proteins, such as their protein–protein interaction domains, tend to be less similar. The specificity of gene regulation depends on chemical interactions between the side chains of amino acids and chemical groups on DNA bases.