title: Stoichiometric and steric principles governing repression by nuclear hormone receptors.
abstract: We have defined two principles of corepressor function that account for differences in transcriptional repression by nuclear hormone receptors (NHRs). First, we have determined that receptor stoichiometry is a crucial determinant of transcriptional repression mediated by the corepressors N-CoR and SMRT. This provides a molecular explanation for the observation that NHRs repress transcription as dimers but not monomers. Second, corepressor function is restricted by steric effects related to DNA binding in a receptor-specific manner. Thus, although N-CoR and SMRT are capable of binding to several NHRs in solution, they are highly selective about receptor binding on DNA, a context that reflects their in vivo function more accurately. These stoichiometric and steric principles govern specific interactions between corepressors and NHRs, thus providing evidence that N-CoR and SMRT do not serve redundant functions but rather contribute to receptor-specific transcriptional repression.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: I
authors.initials: I
authors.lastname: Zamir
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: M A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors