Extensive Variation in Chromatin States Across Humans

被引：261

作者：

Kasowski, Maya ^{[1
,2
]}

Kyriazopoulou-Panagiotopoulou, Sofia ^{[3
]}

Grubert, Fabian ^{[1
]}

Zaugg, Judith B. ^{[1
]}

Kundaje, Anshul ^{[1
,3
,4
,5
]}

Liu, Yuling ^{[8
]}

Boyle, Alan P. ^{[1
]}

Zhang, Qiangfeng Cliff ^{[1
]}

Zakharia, Fouad ^{[1
]}

Spacek, Damek V. ^{[1
]}

Li, Jingjing ^{[1
]}

Xie, Dan ^{[1
]}

Olarerin-George, Anthony ^{[6
]}

Steinmetz, Lars M. ^{[1
,7
]}

Hogenesch, John B. ^{[6
]}

Kellis, Manolis ^{[4
,5
]}

Batzoglou, Serafim ^{[3
]}

Snyder, Michael ^{[1
]}

机构：

[1] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[2] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA

[3] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

[4] MIT, Dept Comp Sci, Cambridge, MA 02139 USA

[5] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[6] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA

[7] European Mol Biol Lab, D-69117 Heidelberg, Germany

[8] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

来源：

SCIENCE | 2013年 / 342卷 / 6159期

基金：

美国国家科学基金会;

关键词：

TRANSCRIPTION FACTOR-BINDING; GENOME-WIDE ASSOCIATION; GENETIC-ANALYSIS;

D O I：

10.1126/science.1242510

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：

The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

引用

页码：750 / 752

页数：3

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