科學家繪製出人類DNase I超敏位點的索引圖譜
作者：
小柯機器人發布時間：2020/8/2 23:59:17
美國華盛頓大學John Stamatoyannopoulos、Wouter Meuleman等研究人員合作繪製出人類DNase I超敏位點（DHS）的索引圖譜。這一研究成果於2020年7月29日發表在《自然》上。
研究人員從733種人體生物樣本中創建了DHS高解析度圖譜，其涵蓋了438個細胞和組織的類型和狀態，並且研究人員將這些圖譜整合在一起，勾勒出人類基因組序列中約360萬個DHS並對其進行了數字索引，從而為調節DNA提供了一個通用坐標。
研究人員發現，這些圖譜高度解析了人類基因組的順式調控區室，這些區室以非常高的密度編碼多種細胞和組織選擇性調控程序。這些程序可以通過簡單的系統進行全面捕獲，並且這一系統可以將包含其組織表現的調節條形碼分配給每個DHS，並以與基因表達正交的方式對蛋白質編碼和非編碼RNA基因進行全局注釋。
最後，研究人員表明，這些DHS顯著增強了疾病和性狀的遺傳關聯和遺傳力信號。研究人員發現，遺傳信號並不僅限於少數遠端元件或啟動子，而是會匯聚在修飾整個基因體的DHS調控集上。總之，這些研究結果為DHS標記的人類調控DNA創建了通用的、可擴展的坐標系統，並為人類基因調控的體系結構提供了新的全局視野。
據悉，DHS是調節性DNA的通用標記，並包含與疾病和表型性狀相關的遺傳變異。
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