Corepressor

In the field of molecular biology, a corepressor is a substance that inhibits the expression of genes. A corepressor downregulates (or represses) the expression of genes not through direct interaction with a gene promoter (a sequence of DNA adjacent to the regulated gene), but rather indirectly through interaction with repressor proteins that in turn bind to the promoter.

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. Hence corepressors prevent binding of coactivators to transcription factors which causes a decrease in gene transcription. 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.

In humans several dozen to several hundred corepressors are known, depending on the level of confidence with which the characterisation of a protein as a corepressors can be made.