A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP
A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP
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DOI：
10.1074/jbc.m700246200
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发表时间：
2007-05-18
影响因子：
4.8
通讯作者：
Khanna, Kum Kum
中科院分区：
文献类型：
--
作者：
Pagan, Julia K.;Arnold, Jeremy;Khanna, Kum Kum
辅抑制子在负基因调控中起着至关重要的作用，在一些疾病中存在缺陷。BCOR是BCL6抑制蛋白的辅阻遏物。这里，我们描述了BCOR的同系物BCOR-L1，并对其进行了功能表征。当与异源启动子结合时，BCOR-L1具有很强的抑制作用。与其他辅抑制子一样，BCOR-L1与组蛋白脱乙酰酶(HDAC)活性有关。具体地说，BCOR-L1与第二类HDACs、HDAC4、HDAC5和HDAC7共沉淀，表明它们参与了BCOR-L1作为转录抑制因子的作用。BCOR-L1还通过其氨基末端的CtBP相互作用基序与CtBP辅阻遏子相互作用。取消BCOR-L1内的CtBP结合位点部分解除了BCOR-L1介导的转录抑制。此外，BCOR-L1位于E-钙粘蛋白启动子上，这是一个已知的CtBP调节启动子，并在报告实验中抑制E-钙粘蛋白启动子的活性。通过RNA介导的干扰抑制BCOR-L1的表达，导致不正常表达E-钙粘素的细胞中E-钙粘蛋白的去抑制，表明BCOR-L1有助于抑制真正的内源性CtBP靶标。
Corepressors play a crucial role in negative gene regulation and are defective in several diseases. BCoR is a corepressor for the BCL6 repressor protein. Here we describe and functionally characterize BCoR-L1, a homolog of BCoR. When tethered to a heterologous promoter, BCoR-L1 is capable of strong repression. Like other corepressors, BCoR-L1 associates with histone deacetylase ( HDAC) activity. Specifically, BCoR-L1 coprecipitates with the Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its role as a transcriptional repressor. BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Abrogation of the CtBP binding site within BCoR-L1 partially relieves BCoR-L1-mediated transcriptional repression. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay. The inhibition of BCoR-L1 expression by RNA-mediated interference results in derepression of E-cadherin in cells that do not normally express E-cadherin, indicating that BCoR-L1 contributes to the repression of an authentic endogenous CtBP target.