The role of histone deacetylase 3 complex in nuclear hormone receptor action

Abstract

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 core-pressors 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‐canoni-cal mechanisms of HDAC3 action are discussed.