CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex
CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex
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DOI：
10.1073/pnas.96.1.23
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发表时间：
1999-01-05
影响因子：
11.1
通讯作者：
Hayward, SD
中科院分区：
文献类型：
--
作者：
Hsieh, JJD;Zhou, SF;Hayward, SD
CBF1是DNA结合因子CSL家族的一员，介导转录抑制或转录激活。CSL蛋白在Notch信号传导和Epstein-Barr病毒诱导的永生化中发挥核心作用。Notch是一种参与细胞命运决定的跨膜蛋白，Notch的细胞质结构域（NotchIC）靶向CBF1。eb - barr病毒永生化蛋白EBNA2通过靶向CBF1和模仿NotchIC激活细胞和病毒基因表达。我们研究了CBF1介导的抑制机制，并表明CBF1与一种独特的协同抑制因子CBF1相互作用协同抑制因子（CIR）结合。秀丽隐杆线虫编码了一个CIR同源物，表明CIR具有进化保守性。两个不能结合CIR的CBF1突变体没有发挥抑制作用，这表明CIR靶向CBF1是抑制的重要组成部分。当作为GaI4融合蛋白表达时，CIR抑制报告基因的表达。CIR结合组蛋白去乙酰化酶和SAP30，并作为CBF1和组蛋白去乙酰化酶复合物之间的连接体。
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 GaI4 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.