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Mol Cell. 2006 Oct 6;24(1):1-11.

Rheostat control of gene expression by metabolites.

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Gene Expression Unit and Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.


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.

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