Coregulators of VDR-mediated gene expression

摘要: Publisher Summary Gene expression is a complex process involving the coordinated repression and activation of transcription. According to simplified two-step model nuclear hormone signaling, unliganded vitamin D receptors (VDR), like other (NRs), are DNA-bound complexed with corepressor molecules that keep chromatin condensed promoter inaccessible transcription machinery. Upon binding 1,25(OH)2D3, corepressors displaced by coactivators begin transcriptional process. Immunodepletion, dominant negative, knockdown, knockout approaches indicate steroid receptor (SRCs), Mediator-D, NCoA62/SKIP have different functions all required for robust VDR-mediated Promoter-specific more global genomic immunoprecipitation (ChIP) strategies provided detailed view into temporal spatial details diverse NR coregulator assembly onto 1,25(OH)2D3-responsive promoters. More recent work indicates yet another level complexity this evolving involvement in These studies suggest switch between gene cannot be simply defined alternative recruitment two regulatory complexes. A realistic continuous cycling or exchange coactivator complexes (on order approximately 60 minutes) 1,25(OH)2D3 activated