Population Variation and Genetic Control of Modular Chromatin Architecture in Humans

被引：164

作者：

Waszak, Sebastian M. ^{[1
,2
]}

Delaneau, Olivier ^{[2
,3
,4
]}

Gschwind, Andreas R. ^{[2
,5
]}

Kilpinen, Helena ^{[2
,3
,4
]}

Raghav, Sunil K. ^{[1
]}

Witwicki, Robert M. ^{[5
]}

Orioli, Andrea ^{[5
]}

Wiederkehr, Michael ^{[5
]}

Panousis, Nikolaos I. ^{[2
,3
,4
]}

Yurovsky, Alisa ^{[2
,3
,4
]}

Romano-Palumbo, Luciana ^{[3
]}

Planchon, Alexandra ^{[3
]}

Bielser, Deborah ^{[3
]}

Padioleau, Ismael ^{[2
,3
,4
]}

Udin, Gilles ^{[1
]}

Thurnheer, Sarah ^{[6
]}

Hacker, David ^{[6
]}

Hernandez, Nouria ^{[5
]}

Reymond, Alexandre ^{[5
]}

Deplancke, Bart ^{[1
,2
]}

Dermitzakis, Emmanouil T. ^{[2
,3
,4
]}

机构：

[1] Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland

[2] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[3] Univ Geneva, Dept Genet Med & Dev, Sch Med, CH-1211 Geneva, Switzerland

[4] Univ Geneva, Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland

[5] Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland

[6] Ecole Polytech Fed Lausanne, Sch Life Sci, Prot Express Core Facil, CH-1015 Lausanne, Switzerland

来源：

CELL | 2015年 / 162卷 / 05期

基金：

欧洲研究理事会; 瑞士国家科学基金会; 日本科学技术振兴机构;

关键词：

TRANSCRIPTION FACTOR-BINDING; HUMAN GENOME; HISTONE MODIFICATIONS; REGULATORY VARIATION; SEQUENCE VARIATION; EVOLUTION; DISEASE; CELLS; DNA; IDENTIFICATION;

D O I：

10.1016/j.cell.2015.08.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.

引用

页码：1039 / 1050

页数：12

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