Cohesin mediates transcriptional insulation by CCCTC-binding factor
Cohesin mediates transcriptional insulation by CCCTC-binding factor
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DOI：
10.1038/nature06634
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发表时间：
2008-02-14
期刊：
影响因子：
64.8
通讯作者：
Peters, Jan-Michael
中科院分区：
文献类型：
--
作者：
Wendt, Kerstin S.;Yoshida, Keisuke;Peters, Jan-Michael
凝聚素复合物介导分裂细胞中的姐妹染色单体凝聚，但也可能有助于有丝分裂后细胞中的基因调控。粘蛋白如何调节基因表达尚不清楚。在这里，我们描述了人类基因组中的粘附素结合位点，并表明其中大部分与CCCTC结合因子（CTCF），一种转录绝缘所需的锌指蛋白有关。CTCF被用于将粘附素加载到DNA上，但需要在特异性结合位点富集粘附素。粘着蛋白使CTCF能够将启动子与远端增强子隔离并控制H19/IGF 2（胰岛素样生长因子2）基因座处的转录。这种作用的凝聚似乎是独立的凝聚力的作用。我们提出，凝聚作为一个转录绝缘子的功能，并推测，在这个功能的微妙缺陷有助于“凝聚病”，如科尔内利亚德兰格综合征。
Cohesin complexes mediate sister- chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin- binding sites in the human genome and show that most of these are associated with the CCCTC- binding factor ( CTCF), a zinc- finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 ( insulin- like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.