Small Molecules Regulate Expression of Many Bacterial Genes via DNA-Binding Repressors and Activators

Transcription of most E. coli genes is regulated by processes similar to those described for the lac operon, although the detailed interactions differ at each promoter. The general mechanism involves a specific repressor that binds to the operator region of a gene or operon, thereby blocking transcription initiation. A small-molecule ligand binds to the repressor controlling its DNA-binding activity, and consequently the frequency of transcription initiation and therefore the rate of synthesis of the mRNA and encoded proteins as appropriate for the needs of the cell. As for the lac operon, many eubacterial transcription-control regions contain one or more secondary operators that contribute to the level of repression.

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Specific activator proteins, such as CAP in the lac operon, also control transcription of a subset of bacterial genes that have binding sites for the activator. Like CAP, other activators bind to DNA together with RNA polymerase, stimulating transcription from a specific promoter. The DNA-binding activity of an activator can be modulated in response to cellular needs by the binding of specific small-molecule ligands (e.g., cAMP) or by post-translational modifications, such as phosphorylation, that alter the conformation of the activator.