title: A nuclear hormone receptor corepressor mediates transcriptional silencing by receptors with distinct repression domains.
abstract: Ligand-independent transcriptional repression is an important function of nuclear hormone receptors. An interaction screen with the repression domain of the orphan receptor RevErb identified N-CoR, the corepressor for thyroid hormone receptor (TR) and retinoic acid receptor (RAR). N-CoR is likely to be a bona fide transcriptional corepressor for RevErb because (i) RevErb interacts with endogenous N-CoR, (ii) ectopic N-CoR potentiates RevErb-mediated repression, and (iii) transcriptional repression by RevErb correlates with its ability to bind N-CoR. Remarkably, a region homologous to the CoR box which is necessary for TR and RAR to interact with N-CoR is not required for RevErb. Rather, two short regions of RevErb separated by approximately 200 amino acids are required for interaction with N-CoR. The primary amino acid sequence of the N-terminal region of RevErb essential for N-CoR interaction is not homologous to that of TR or RAR, whereas similarities exist among the C-terminal domains of the receptors. N-CoR contains two adjacent but distinct interaction domains, one of which binds tightly to both RevErb and TR whereas the other binds more weakly and differentially interacts with the nuclear receptors. These results indicate that multiple nuclear receptors, utilizing different primary amino acid sequences, repress transcription by interacting with N-CoR.
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: H P
authors.initials: HP
authors.lastname: Harding
authors.forename: G B
authors.initials: GB
authors.lastname: Atkins
authors.forename: A
authors.initials: A
authors.lastname: Hörlein
authors.forename: C K
authors.initials: CK
authors.lastname: Glass
authors.forename: M G
authors.initials: MG
authors.lastname: Rosenfeld
authors.forename: M A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017124:Conserved Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D004926:Escherichia coli; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D007668:Kidney; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000737:chemistry; D011988:Receptors, Thyroid Hormone / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C000607071:RARA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000072482:Retinoic Acid Receptor alpha; D005982:Glutathione Transferase