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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. ladurner@embl.de


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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