Nuclear hormone receptors (NRs) regulate transcription of the target genes in a ligand-dependent manner in either a positive or negative direction, depending on the case. Deacetylation of histone tails is associated with transcriptional repression. A nuclear receptor corepressor (N-CoR) and a silencing mediator for retinoid and thyroid hormone receptors (SMRT) are the main corepressors responsible for gene suppression mediated by NRs. Among numerous histone deacetylases (HDACs), HDAC3 is the core component of the N-CoR/SMRT complex, and plays a central role in NR-dependent repression. Here, the roles of HDAC3 in ligand-independent repression, gene repression by orphan NRs, NRs antagonist action, ligand-induced repression, and the activation of a transcriptional coactivator are reviewed. In addition, some perspectives regarding the non-canonical mechanisms of HDAC3 action are discussed.
Keywords: histone deacetylase 3; nuclear hormone receptor; nuclear receptor corepressor; silencing mediator for retinoid and thyroid hormone receptors.