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The accessible chromatin landscape of the human genome

机译：人类基因组的易染色质景观

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摘要

DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ～2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect ～580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular Dnase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation.
机译：DNase I超敏位点（DHS）是调节DNA的标记，并支持所有类型的顺式调节元件的发现，包括增强子，启动子，绝缘子，沉默子和基因座控制区。在这里，我们展示了人类DHS的第一张广泛的图谱，该图谱是通过在125种不同细胞和组织类型中进行全基因组分布分析而确定的。我们确定了约290万个DHS，它们几乎涵盖了所有已知的经过实验验证的顺式调控序列，并揭示了大量新颖的元素，其中大多数具有高度的细胞选择性调控。使用ENCODE数据注释这些元素揭示了染色质可访问性，转录，DNA甲基化和调节因子占用模式之间的新颖关系。我们将约580,000个远端DHS与它们的靶标启动子连接起来，揭示了不同类别的远端DHS和特定启动子类型的系统配对。染色质可及性在许多调控区域的模式都由数十到数百个共同激活的元素组成，并且在给定区域的跨细胞Dnase I敏感性模式可以预测细胞类型的特定功能行为。 DHS格局显示了近期功能进化约束的特征。然而，多能和永生化细胞中的DHS区室比高分化细胞中的DHS区室具有更高的突变率，从而揭示了染色质可及性，增殖潜力和人类变异模式之间的意外联系。

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  • 来源
    《Nature》 |2012年第7414期|p.75-82|共8页
  • 作者

    Robert E. Thurman; Eric Rynes; Richard Humbert; Jeff Vierstra; Matthew T. Maurano; et al;

  • 作者单位

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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