title: CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex.
abstract: CBF1 is a member of the CSL family of DNA binding factors, which mediate either transcriptional repression or transcriptional activation. CSL proteins play a central role in Notch signaling and in Epstein-Barr virus-induced immortalization. Notch is a transmembrane protein involved in cell-fate decisions, and the cytoplasmic domain of Notch (NotchIC) targets CBF1. The Epstein-Barr virus-immortalizing protein EBNA2 activates both cellular and viral gene expression by targeting CBF1 and mimicking NotchIC. We have examined the mechanism of CBF1-mediated repression and show that CBF1 binds to a unique corepressor, CBF1 interacting corepressor (CIR). A CIR homolog is encoded by Caenorhabditis elegans, indicating that CIR is evolutionarily conserved. Two CBF1 mutants that were unable to bind CIR did not function as repressors, suggesting that targeting of CIR to CBF1 is an important component of repression. When expressed as a Gal4 fusion protein, CIR repressed reporter gene expression. CIR binds to histone deacetylase and to SAP30 and serves as a linker between CBF1 and the histone deacetylase complex.
authors.affiliation: Molecular Virology Laboratories, Department of Pharmacology and Molecular Sciences and Department of Oncology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Hsieh
authors.forename: S
authors.initials: S
authors.lastname: Zhou
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: D B
authors.initials: DB
authors.lastname: Young
authors.forename: S D
authors.initials: SD
authors.lastname: Hayward
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans; D002467:Cell Nucleus / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells
chemical_list: C117385:CIR1 protein, human; D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; C497570:RBPJ protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C113294:SAP30 protein, human; D006655:Histone Deacetylases