In the field of molecular biology, a corepressor is a substance that inhibits the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, but instead indirectly regulates gene expression by binding to repressors.
A corepressor downregulates (or represses) the expression of genes by binding to and activating a repressor transcription factor. The repressor in turn binds to a gene promoter (a sequence of DNA adjacent to the regulated gene), thereby blocking transcription of that gene.
In prokaryotes, the term corepressor is used to denote the activating ligand of a repressor protein. For example, the E. coli tryptophan repressor (TrpR) is only able to bind to DNA and repress transcription of the trp operon when its corepressor tryptophan is bound to it. TrpR in the absence of tryptophan is known as an aporepressor and is inactive in repressing gene transcription. Trp operon encodes enzymes responsible for the synthesis of tryptophan. Hence TrpR provides a negative feedback mechanism that regulates the biosynthesis of tryptophan.
In eukaryotes, a corepressor is a protein that binds to transcription factors. In the absence of corepressors and in the presence of coactivators, transcription factors upregulate gene expression. Coactivators and corepressors compete for the same binding sites on transcription factors. A second mechanism by which corepressors may repress transcriptional initiation when bound to transcription factor/DNA complexes is by recruiting histone deacetylases which catalyze the removal of acetyl groups from lysine residues. This increases the positive charge on histones which strengthens the electrostatic attraction between the positively charged histones and negatively charged DNA, making the DNA less accessible for transcription.
- Evans PD, Jaseja M, Jeeves M, Hyde EI (December 1996). "NMR studies of the Escherichia coli Trp repressor.trpRs operator complex". Eur. J. Biochem. 242 (3): 567–75. doi:10.1111/j.1432-1033.1996.0567r.x. PMID 9022683.
- Foster JB, Slonczewski J (2010). Microbiology: An Evolving Science (Second ed.). New York: W. W. Norton & Company. ISBN 0-393-93447-0.
- Jenster G (August 1998). "Coactivators and corepressors as mediators of nuclear receptor function: an update". Mol. Cell. Endocrinol. 143 (1-2): 1–7. doi:10.1016/S0303-7207(98)00145-2. PMID 9806345.
- Lazar MA (2003). "Nuclear receptor corepressors". Nucl Recept Signal. 1: e001. doi:10.1621/nrs.01001. PMC 1402229. PMID 16604174.
- Goodson M, Jonas BA, Privalsky MA (2005). "Corepressors: custom tailoring and alterations while you wait". Nucl Recept Signal. 3 (Oct 21): e003. doi:10.1621/nrs.03003. PMC 1402215. PMID 16604171.
- Schaefer U, Schmeier S, Bajic VB (January 2011). "TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins". Nucleic Acids Res. 39 (Database issue): D106–10. doi:10.1093/nar/gkq945. PMC 3013796. PMID 20965969.