Coordinated Effects of Sequence Variation on DNA Binding, Chromatin Structure, and Transcription

被引：262

作者：

Kilpinen, Helena ^{[1
,2
,3
]}

Waszak, Sebastian M. ^{[2
,4
]}

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

Raghav, Sunil K. ^{[4
]}

Witwicki, Robert M. ^{[5
]}

Orioli, Andrea ^{[5
]}

Migliavacca, Eugenia ^{[2
,5
]}

Wiederkehr, Michael ^{[5
]}

Gutierrez-Arcelus, Maria ^{[1
,2
,3
]}

Panousis, Nikolaos I. ^{[1
,2
,3
]}

Yurovsky, Alisa ^{[1
,2
,3
]}

Lappalainen, Tuuli ^{[1
,2
,3
]}

Romano-Palumbo, Luciana ^{[1
]}

Planchon, Alexandra ^{[1
]}

Bielser, Deborah ^{[1
]}

Bryois, Julien ^{[1
,2
,3
]}

Padioleau, Ismael ^{[1
,2
,3
]}

Udin, Gilles ^{[4
]}

Thurnheer, Sarah ^{[6
]}

Hacker, David ^{[6
]}

Core, Leighton J. ^{[7
]}

Lis, John T. ^{[7
]}

Hernandez, Nouria ^{[5
]}

Reymond, Alexandre ^{[5
]}

Deplancke, Bart ^{[2
,4
]}

Dermitzakis, Emmanouil T. ^{[1
,2
,3
,8
]}

机构：

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

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

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

[4] Swiss Fed Inst Technol EPFL, Sch Life Sci, Inst Bioengn, Lab Syst Biol & Genet, CH-1015 Lausanne, Switzerland

[5] Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1011 Lausanne, Switzerland

[6] Swiss Fed Inst Technol EPFL, Sch Life Sci, Prot Express Core Facil, CH-1015 Lausanne, Switzerland

[7] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14850 USA

[8] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21589, Saudi Arabia

来源：

SCIENCE | 2013年 / 342卷 / 6159期

基金：

欧洲研究理事会; 日本科学技术振兴机构; 瑞士国家科学基金会;

关键词：

D O I：

10.1126/science.1242463

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：

DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.

引用

页码：744 / 747

页数：4

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