Rheostat control of gene expression by metabolites.

Organisms adapt to changes in environmental conditions by altering gene expression. Such homeostatic control is apparent in metabolism, where biosynthetic metabolites play a role in regulatory feedback loops. Increasing evidence shows that small-molecule metabolites also shape the structure of chromatin and directly regulate the transcription and translation processes. These endogenous metabolites bind specialized histones, are used as substrates by chromatin-modifying enzymes, regulate the activity of transcriptional corepressors, and even modulate the structure of RNA itself. In doing so, they act as dynamic rheostats that fine-tune the activity of hard-wired gene circuits. Metabolites emerge as key effectors in tweaking gene expression.