Mediator and cohesin connect gene expression and chromatin architecture.

Mediator and cohesin connect gene expression and chromatin architecture.
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DOI:
10.1038/nature09380
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发表时间:
2010-09-23
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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转录因子通过与不同的辅活化子和转录装置相互作用来控制细胞特有的基因表达程序。基因激活可能涉及增强子结合的转录因子和核心启动子上的转录装置之间的DNA环形成,但这一过程尚不清楚。我们在这里报道,在胚胎干细胞中,介体和粘附素在物理上和功能上连接着活性基因的增强子和核心启动子。介体是一种转录共激活因子,它与粘附素形成复合体,可以形成连接两个DNA片段的环。粘附素加载因子Nipb1与介体/粘附素复合体相关,提供了一种在启动子上加载粘附素的方法。在中介体和粘附素占据的增强子和启动子之间观察到DNA环。介体和粘附素在不同的细胞中占据不同的启动子,从而产生与每个细胞的基因表达程序相联系的细胞型特异性DNA环。
Transcription factors control cell specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. We report here that Mediator and Cohesin physically and functionally connect the enhancers and core promoters of active genes in embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with Cohesin, which can form rings that connect two DNA segments. The Cohesin loading factor Nipbl is associated with Mediator/Cohesin complexes, providing a means to load Cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by Mediator and Cohesin. Mediator and Cohesin occupy different promoters in different cells, thus generating cell-type specific DNA loops linked to the gene expression program of each cell.
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