Coactivators and corepressors as mediators of nuclear receptor function: An update

The past 3 years have been an exciting time in the field of hormone receptor research because of the discovery and characterization of novel groups of proteins that mediate the transcriptional activity of steroid receptors. These classes of proteins, called coactivators and corepressors, have greatly enhanced our understanding of how steroid receptors activate or inhibit transcription of their target genes. Multiple coactivators have been identified that fit the definition of a protein that connects or bridges the DNA-bound receptor to proteins in the preinitiation complex and thereby enhance transcription. Besides this bridging function, some coactivators can modify chromatin by histone acetylation and make promoters more accessible for the binding of other transcription factors. This finding explains old data concerning steroid receptor-induced nucleosome displacement and indicates a dual role for coactivators as bridging factors and chromatin remodeling proteins. The opposites of coactivators are corepressors, which are recruited into the receptor-DNA-bound complex in the absence of ligand and actively inhibit transcription of the target gene. Although unliganded steroid receptors are associated with heal shock proteins and do not bind to their response elements, the binding of antagonists to these receptors can result in the recruitment of corepressors. The expression level and repertoire of coactivators and corepressors have become important determinants in the functional activity of steroid hormones and their receptors. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.