DNase I hypersensitive sites (DHSs) are generic markers of regulatory DNA 1 – 5 and contain genetic variations associated with diseases and phenotypic traits 6 – 8 . We created high-resolution maps of DHSs from 733 human biosamples encompassing 438 cell and tissue types and states, and integrated these to delineate and numerically index approximately 3.6 million DHSs within the human genome sequence, providing a common coordinate system for regulatory DNA. Here we show that these maps highly resolve the cis -regulatory compartment of the human genome, which encodes unexpectedly diverse cell- and tissue-selective regulatory programs at very high density. These programs can be captured comprehensively by a simple vocabulary that enables the assignment to each DHS of a regulatory barcode that encapsulates its tissue manifestations, and global annotation of protein-coding and non-coding RNA genes in a manner orthogonal to gene expression. Finally, we show that sharply resolved DHSs markedly enhance the genetic association and heritability signals of diseases and traits. Rather than being confined to a small number of distal elements or promoters, we find that genetic signals converge on congruently regulated sets of DHSs that decorate entire gene bodies. Together, our results create a universal, extensible coordinate system and vocabulary for human regulatory DNA marked by DHSs, and provide a new global perspective on the architecture of human gene regulation. High-resolution maps of DNase I hypersensitive sites from 733 human biosamples are used to identify and index regulatory DNA within the human genome.

中文翻译：

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人类 DNase I 超敏位点的索引和生物谱

DNase I 超敏位点 (DHS) 是调节性 DNA 1-5 的通用标记，包含与疾病和表型特征相关的遗传变异 6-8。我们从包含 438 种细胞和组织类型和状态的 733 个人类生物样本中创建了 DHS 的高分辨率图谱，并将这些图整合到人类基因组序列中描绘和数字索引大约 360 万个 DHS，为调节 DNA 提供了一个通用坐标系。在这里，我们展示了这些图谱高度解析了人类基因组的顺式调节区室，该区室以非常高的密度编码出乎意料的多样化细胞和组织选择性调节程序。这些程序可以通过一个简单的词汇表全面捕获，该词汇表可以将封装其组织表现的监管条形码分配给每个 DHS，以与基因表达正交的方式对蛋白质编码和非编码 RNA 基因进行全局注释。最后，我们表明清晰解析的 DHS 显着增强了疾病和性状的遗传关联和遗传信号。我们发现遗传信号并不局限于少数远端元件或启动子，而是集中在装饰整个基因体的一致调节的 DHS 集上。总之，我们的结果为由 DHS 标记的人类调控 DNA 创建了一个通用的、可扩展的坐标系统和词汇，并为人类基因调控的架构提供了一个新的全球视角。来自 733 个人类生物样本的 DNase I 超敏位点的高分辨率图用于识别和索引人类基因组中的调节 DNA。