Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks

被引：43

作者：

Choy, Mun-Kit ^{[1
]}

Javierre, Biola M. ^{[2
,3
]}

Williams, Simon G. ^{[1
]}

Baross, Stephanie L. ^{[1
]}

Liu, Yingjuan ^{[1
]}

Wingett, Steven W. ^{[2
]}

Akbarov, Artur ^{[1
]}

Wallace, Chris ^{[4
,5
]}

Freire-Pritchett, Paula ^{[2
,6
]}

Rugg-Gunn, Peter J. ^{[7
]}

Spivakov, Mikhail ^{[2
]}

Fraser, Peter ^{[2
,8
]}

Keavney, Bernard D. ^{[1
]}

机构：

[1] Univ Manchester, Div Cardiovasc Sci, Manchester M13 9PT, Lancs, England

[2] Babraham Inst, Nucl Dynam Programme, Cambridge CB22 3AT, England

[3] Josep Carreras Leukaemia Res Inst, Campus ICO Germans Trias & Pujol, Barcelona 08916, Spain

[4] Univ Cambridge, MRC, Biostat Unit, Cambridge CB2 0SR, England

[5] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England

[6] MRC, Lab Mol Biol, Div Cell Biol, Cambridge CB2 0QH, England

[7] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England

[8] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; ENDOTHELIN RECEPTOR; REGULATORY ELEMENTS; EXPRESSION; VARIANTS; CHANNELS; LOCI;

D O I：

10.1038/s41467-018-04931-0

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：

Long-range chromosomal interactions bring distal regulatory elements and promoters together to regulate gene expression in biological processes. By performing promoter capture Hi-C (PCHi-C) on human embryonic stem cell-derived cardiomyocytes (hESC-CMs), we show that such promoter interactions are a key mechanism by which enhancers contact their target genes after hESC-CM differentiation from hESCs. We also show that the promoter interactome of hESC-CMs is associated with expression quantitative trait loci (eQTLs) in cardiac left ventricular tissue; captures the dynamic process of genome reorganisation after hESC-CM differentiation; overlaps genome-wide association study (GWAS) regions associated with heart rate; and identifies new candidate genes in such regions. These findings indicate that regulatory elements in hESC-CMs identified by our approach control gene expression involved in ventricular conduction and rhythm of the heart. The study of promoter interactions in other hESC-derived cell types may be of utility in functional investigation of GWAS-associated regions.

引用

页数：10

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