title: Transcriptional silencing is defined by isoform- and heterodimer-specific interactions between nuclear hormone receptors and corepressors.
abstract: Nuclear hormone receptors are ligand-regulated transcription factors that play critical roles in metazoan homeostasis, development, and reproduction. Many nuclear hormone receptors exhibit bimodal transcriptional properties and can either repress or activate the expression of a given target gene. Repression appears to require a physical interaction between a receptor and a corepressor complex containing the SMRT/TRAC or N-CoR/RIP13 polypeptides. We wished to better elucidate the rules governing the association of receptors with corepressors. We report here that different receptors interact with different domains in the SMRT and N-CoR corepressors and that these divergent interactions may therefore contribute to distinct repression phenotypes. Intriguingly, different isoforms of a single nuclear hormone receptor class also differ markedly in their interactions with corepressors, indicative of their nonidentical actions in cellular regulation. Finally, we present evidence that combinatorial interactions between different receptors can, through the formation of heterodimeric receptors, result in novel receptor-corepressor interactions not observed for homomeric receptors.
authors.affiliation: Section of Microbiology, Division of Biological Sciences, University of California at Davis, Davis, California 95616, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Wong
authors.forename: M L
authors.initials: ML
authors.lastname: Privalsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014158:Transcription, Genetic; D000097768:Retinoic Acid Receptor gamma
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; C000607071:RARA protein, human; C082925:retinoic acid receptor beta