Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks.
Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks.
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DOI：
10.1038/s41467-018-04931-0
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发表时间：
2018-06-28
影响因子：
16.6
通讯作者：
Keavney BD
中科院分区：
文献类型：
--
作者：
Choy MK;Javierre BM;Williams SG;Baross SL;Liu Y;Wingett SW;Akbarov A;Wallace C;Freire-Pritchett P;Rugg-Gunn PJ;Spivakov M;Fraser P;Keavney BD
在生物学过程中，染色体长距离相互作用将远端调控元件和启动子结合在一起以调控基因表达。通过对人胚胎干细胞衍生的心肌细胞（hESC-CM）进行启动子捕获Hi-C（PCHi-C），我们表明，这种启动子相互作用是hESC-CM从hESC分化后增强子接触其靶基因的关键机制。我们还表明，hESC-CM的启动子相互作用组与心脏左心室组织中的表达数量性状位点（eQTL）相关;捕获hESC-CM分化后基因组重组的动态过程;与心率相关的全基因组关联研究（GWAS）区域重叠;并在这些区域中识别新的候选基因。这些发现表明，通过我们的方法确定的hESC-CM中的调节元件控制参与心室传导和心脏节律的基因表达。在其他人胚胎干细胞衍生的细胞类型的启动子相互作用的研究可能是实用的GWAS相关区域的功能研究。人胚胎干细胞衍生的心肌细胞（hESC-CM）是一种广泛应用于心脏基因组学研究的模型。在此，Choy等人进行启动子捕获Hi-C以绘制hESC-CM的长程染色体相互作用，并研究这些区域与心脏表型相关的遗传基因座的重叠。
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. Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are a widely used model to study cardiac genomics. Here, Choy et al. perform promoter capture Hi-C to map long-range chromosomal interactions of hESC-CMs and to study overlap of such regions with genetic loci associated with cardiac phenotypes.
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影响因子：
64.8
作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
7.7
作者：
Freire-Pritchett P;Schoenfelder S;Várnai C;Wingett SW;Cairns J;Collier AJ;García-Vílchez R;Furlan-Magaril M;Osborne CS;Fraser P;Rugg-Gunn PJ;Spivakov M
通讯作者：
Spivakov M
影响因子：
3.7
作者：
Busser BW;Lin Y;Yang Y;Zhu J;Chen G;Michelson AM
通讯作者：
Michelson AM
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
30.8
作者：
Mifsud, Borbala;Tavares-Cadete, Filipe;Osborne, Cameron S.
通讯作者：
Osborne, Cameron S.