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科学家绘制出人类DNase I超敏位点的索引图谱
2020-08-02 23:59

美国华盛顿大学John Stamatoyannopoulos、Wouter Meuleman等研究人员合作绘制出人类DNase I超敏位点(DHS)的索引图谱。这一研究成果于2020年7月29日发表在《自然》上。

研究人员从733种人体生物样本中创建了DHS高分辨率图谱,其涵盖了438个细胞和组织的类型和状态,并且研究人员将这些图谱整合在一起,勾勒出人类基因组序列中约360万个DHS并对其进行了数字索引,从而为调节DNA提供了一个通用坐标。
 
研究人员发现,这些图谱高度解析了人类基因组的顺式调控区室,这些区室以非常高的密度编码多种细胞和组织选择性调控程序。这些程序可以通过简单的系统进行全面捕获,并且这一系统可以将包含其组织表现的调节条形码分配给每个DHS,并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,研究人员表明,这些DHS显著增强了疾病和性状的遗传关联和遗传力信号。研究人员发现,遗传信号并不仅限于少数远端元件或启动子,而是会汇聚在修饰整个基因体的DHS调控集上。总之,这些研究结果为DHS标记的人类调控DNA创建了通用的、可扩展的坐标系统,并为人类基因调控的体系结构提供了新的全局视野。
 
据悉,DHS是调节性DNA的通用标记,并包含与疾病和表型性状相关的遗传变异。
 
附:英文原文

Title: Index and biological spectrum of human DNase I hypersensitive sites

Author: Wouter Meuleman, Alexander Muratov, Eric Rynes, Jessica Halow, Kristen Lee, Daniel Bates, Morgan Diegel, Douglas Dunn, Fidencio Neri, Athanasios Teodosiadis, Alex Reynolds, Eric Haugen, Jemma Nelson, Audra Johnson, Mark Frerker, Michael Buckley, Richard Sandstrom, Jeff Vierstra, Rajinder Kaul, John Stamatoyannopoulos

Issue&Volume: 2020-07-29

Abstract: DNase I hypersensitive sites (DHSs) are generic markers of regulatory DNA1,2,3,4,5 and contain genetic variations associated with diseases and phenotypic traits6,7,8. 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.

DOI: 10.1038/s41586-020-2559-3

Source: https://www.nature.com/articles/s41586-020-2559-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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