The accessible chromatin landscape of the human genome

被引：1881

作者：

Thurman, Robert E. ^{[1
]}

Rynes, Eric ^{[1
]}

Humbert, Richard ^{[1
]}

Vierstra, Jeff ^{[1
]}

Maurano, Matthew T. ^{[1
]}

Haugen, Eric ^{[1
]}

Sheffield, Nathan C. ^{[2
]}

Stergachis, Andrew B. ^{[1
]}

Wang, Hao ^{[1
]}

Vernot, Benjamin ^{[1
]}

Garg, Kavita ^{[3
]}

John, Sam ^{[1
]}

Sandstrom, Richard ^{[1
]}

Bates, Daniel ^{[1
]}

Boatman, Lisa ^{[4
]}

Canfield, Theresa K. ^{[1
]}

Diegel, Morgan ^{[1
]}

Dunn, Douglas ^{[1
]}

Ebersol, Abigail K. ^{[4
]}

Frum, Tristan ^{[4
]}

Giste, Erika ^{[1
]}

Johnson, Audra K. ^{[1
]}

Johnson, Ericka M. ^{[4
]}

Kutyavin, Tanya ^{[1
]}

Lajoie, Bryan ^{[5
]}

Lee, Bum-Kyu ^{[6
]}

Lee, Kristen ^{[1
]}

London, Darin ^{[2
]}

Lotakis, Dimitra ^{[4
]}

Neph, Shane ^{[1
]}

Neri, Fidencio ^{[1
]}

Nguyen, Eric D. ^{[4
]}

Qu, Hongzhu ^{[1
,7
]}

Reynolds, Alex P. ^{[1
]}

Roach, Vaughn ^{[1
]}

Safi, Alexias ^{[2
]}

Sanchez, Minerva E. ^{[4
]}

Sanyal, Amartya ^{[5
]}

Shafer, Anthony ^{[1
]}

Simon, Jeremy M. ^{[8
]}

Song, Lingyun ^{[2
]}

Vong, Shinny ^{[1
]}

Weaver, Molly ^{[1
]}

Yan, Yongqi ^{[4
]}

Zhang, Zhancheng ^{[8
]}

Zhang, Zhuzhu ^{[8
]}

Lenhard, Boris ^{[9
,10
]}

Tewari, Muneesh ^{[3
]}

Dorschner, Michael O. ^{[11
]}

Hansen, R. Scott ^{[4
]}

机构：

[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[2] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA

[3] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

[4] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA

[5] Univ Massachusetts, Program Syst Biol, Sch Med, Worcester, MA 01605 USA

[6] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA

[7] Chinese Acad Sci, Lab Dis Genom & Individualized Med, Beijing Inst Genom, Beijing 100029, Peoples R China

[8] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA

[9] Univ Bergen, Dept Biol, N-5008 Bergen, Norway

[10] Univ Bergen, Bergen Ctr Computat Sci, N-5008 Bergen, Norway

[11] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[12] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA

[13] Harvard Univ, Sch Med, Boston, MA 02115 USA

[14] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA

来源：

NATURE | 2012年 / 489卷 / 7414期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

LOCUS-CONTROL REGION; BETA-GLOBIN LOCUS; TRANSCRIPTION; BINDING; DISTINCT; PROTEIN; NF-E2;

D O I：

10.1038/nature11232

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 similar to 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 similar to 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.

引用

页码：75 / 82

页数：8