Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Nature. 2010 Sep 23;467(7314):430-5. doi: 10.1038/nature09380. Epub 2010 Aug 18.
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. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine 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 co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.
转录因子通过与各种共激活因子和转录装置的相互作用来控制细胞特异性基因表达程序。基因激活可能涉及增强子结合转录因子和核心启动子处转录装置之间的 DNA 环形成，但该过程尚不清楚。在这里，我们报告说，在小鼠胚胎干细胞中，中介体和黏合蛋白将活性基因的增强子和核心启动子在物理上和功能上连接起来。中介体是一种转录共激活因子，它与黏合蛋白形成复合物，而黏合蛋白可以形成连接两个 DNA 片段的环。黏合蛋白加载因子 Nipbl 与中介体-黏合蛋白复合物相关联，为在启动子处加载黏合蛋白提供了一种手段。在由中介体和黏合蛋白占据的增强子和启动子之间观察到 DNA 环。在不同的细胞中，中介体和黏合蛋白共同占据不同的启动子，从而产生与每个细胞的基因表达程序相关联的细胞类型特异性 DNA 环。
