The Role of Corepressors in Transcriptional Regulation by Nuclear Hormone Receptors

Abstract

Nuclear receptors (also known as nuclear hormone receptors) are hormone-regulated transcription factors that control many important physiological and developmental processes in animals and humans. Defects in receptor function result in disease. The diverse biological roles of these receptors reflect their surprisingly versatile transcriptional properties, with many receptors possessing the ability to both repress and activate target gene expression. These bipolar transcriptional properties are mediated through the interactions of the receptors with two distinct classes of auxiliary proteins: corepressors and coactivators. This review focuses on how corepressors work together with nuclear receptors to repress gene transcription in the normal organism and on the aberrations in this process that lead to neoplasia and endocrine disorders. The actions of coactivators and the contributions of the same corepressors to the functions of nonreceptor transcription factors are also touched on.

Transient expression of thyroid hormone nuclear receptor TRβ2 sets S opsin patterning during cone photoreceptor genesis

“…Through recruitment of coregulators, they direct chromatin remodeling for repression or activation of their target genes (Germain et al, 2003;Privalsky, 2004;Perissi and Rosenfeld, 2005;Rosenfeld et al, 2006). In general, three modes of action can be considered: (1) in the unliganded state, TR␤2 binds its target DNA and assembles a repression complex; (2) upon binding T3, TR␤2 may recruit a coactivator, which in turn assembles complexes that remodel and open the chromatin state near the transcription start site.…”

Thyroid hormone receptor β1 domains responsible for the antagonism with the ras oncogene: role of corepressors

“…Unliganded TRs associate with corepressors such as nuclear receptor corepressor (NCoR) or silencing mediator of retinoic and thyroid receptor (SMRT) that belong to complexes that contain histone deacetylases and cause chromatin compactation (Lazar, 2003;Privalsky, 2004). Ligand binding allows the release of corepressors and the recruitment of coactivators responsible for chromatin decompactation and transcriptional stimulation.…”

Interactions between the estrogen receptor, its cofactors and microRNAs in breast cancer

“…The majority of those identified are coactivators, recruited by activated, ligand-bound NRs to enhance gene expression, whereas corepressors, of which approximately 40 have been identified, generally interact with unliganded receptors [7] and oppose the actions of coactivators. The balance between coactivators and corepressors defines the outcome of the cellular responses to NR ligands and the switching of corepressors for coactivators can convert a transcription factor from a repressor to an activator of gene expression [8][9][10].…”

“…They possess histone deacetylase activity, which can inhibit the basal transcriptional machinery and the assembly of preinitiation complexes [10,[16][17][18]. In contrast to coactivators, comparatively little is known of the actions of specific corepressors, and a definition of their involvement in transcriptional repression is still emerging.…”

“…In contrast to coactivators, comparatively little is known of the actions of specific corepressors, and a definition of their involvement in transcriptional repression is still emerging. Two better characterized corepressors, which serve as repressors for a large number of transcription factors including the steroid hormone receptors, are the structurally related Nuclear Receptor CoRepressor (N-CoR) and Silencing Mediator of Retinoid and Thyroid Receptor (SMRT) [10,19]. Their structure and function has been comprehensively reviewed elsewhere [15,20,21].…”