CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex

CBF1 is a member of the CSL family of DNA binding factors, which mediate ei ther transcriptional repression or transcriptional activation. CSL proteins play a central role in Notch signaling and in Epstein-Barr virus-induced i mmortalization. Notch is a transmembrane protein involved in cell-fate deci sions, and the cytoplasmic domain of Notch (NotchIC) targets CBF1. The Epst ein-Barr virus-immortalizing protein EBNA2 activates both cellular and vira l gene expression by targeting CBF1 and mimicking NotchIC. We have examined the mechanism of CBF1-mediated repression and show that CBF1 binds to a un ique corepressor, CBF1 interacting corepressor (CIR). A CIR homolog is enco ded by Caenorhabditis elegans, indicating that CIR is evolutionarily conser ved. Two CBF1 mutants that were unable to bind CIR did not function as repr essors, suggesting that targeting of CIR to CBF1 is an important component of repression. When expressed as a GaI4 fusion protein, CIR repressed repor ter gene expression. CIR binds to histone deacetylase and to SAP30 and serv es as a linker between CBF1 and the histone deacetylase complex.