Nuclear receptor coregulators merge transcriptional coregulation with epigenetic regulation

Members of the nuclear steroid/thyroid hormone receptor (NR) gene superfamily are DNA-binding transcription factors that regulate target genes in a spatiotemporal manner, depending on the promoter context. In vivo observations of ligand responses in NR-mediated gene regulation led to the identification of ligand-dependent coregulators that directly interact with NRs. Functional dissection of NR coregulators revealed that their transcriptional coregulation was linked to histone acetylation. However, recent work in the fields of reversible histone modification and chromatin remodeling indicates that histone-modifying enzymes, including histone methylases and chromatin remodelers, are potential transcriptional coregulators that interact directly and indirectly with NRs.