DNase I超敏位点（DHSs）是调节性DNA的标志，它是所有已发现的顺式作用元件的基础，包括增强子、启动子、绝缘子、沉默子以及基因座位控制区。

借助全基因组图谱，本研究首次提供了125种不同细胞和组织类型中的人类DHS的全面分布图。我们鉴定了约290万个DHS，包括了所有已知的经实验验证的顺式调控序列，发现了大量的新元件资源，其中大多数与细胞选择性调控高度相关。利用ENCODE数据对这些元件进行注释，本研究揭示了染色质可及性、转录、DNA甲基化与调控因子占用模式之间的新关系。

我们将约580000个远端DHS与其靶启动子联系起来，揭示了不同类别的远端DHS和特异性启动子类型之间的系统性配对规律。许多调控区域的染色质可及性模式结合了几十到几百个共激活元件，给定区域的跨膜DNase I敏感模式可以预测细胞类型特异性功能行为。

DHS图谱表现出近期功能进化限制的特点。然而，多能细胞和永生细胞中的DHS区室比高度分化细胞中的DHS区室表现出更高的突变率，这展现了染色质可及性、增殖潜力与人类差异模式之间出乎意料的联系。

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The accessible chromatin landscape of the human genome

DOI:10.1038/nature11232

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.

http://www.bio360.net/news/show/3395.html