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Mediator and cohesin connect gene expression and chromatin architecture

机译:介体和粘着蛋白连接基因表达和染色质结构

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摘要

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.
机译: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,但这一过程尚未广为人知。在这里我们报告介导和cohesin物理和功能上连接小鼠胚胎干细胞中的活性基因的增强子和核心启动子。介体,一种转录共激活因子,与粘着蛋白形成复合物,可形成连接两个DNA片段的环。粘附素加载因子Nipb1与介体-粘附素复合物相关,提供了在启动子上加载粘附素的方法。在由介体和粘着蛋白占据的增强子和启动子之间观察到DNA环化。介体和粘着蛋白在不同细胞中共同占据不同的启动子,从而产生与每种细胞的基因表达程序链接的细胞类型特异性DNA环。

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  • 来源
    《Nature》 |2010年第7314期|P.430-435|共6页
  • 作者单位

    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    rnWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    rnWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    rnProgram in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA;

    rnWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    rnProgram in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA;

    rnDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA;

    rnDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA;

    rnWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA;

    rnDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    rnDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA;

    rnProgram in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA;

    rnWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

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