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

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Javierre, Biola M 
Williams, Simon G 
Baross, Stephanie L 
Liu, Yingjuan 


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.



Actinin, Calpain, Cell Differentiation, Cell Line, Enhancer Elements, Genetic, Gene Regulatory Networks, Genome, Human, Genome-Wide Association Study, Heart Conduction System, Heart Rate, Heart Ventricles, Histones, Human Embryonic Stem Cells, Humans, Myocytes, Cardiac, Promoter Regions, Genetic, Protein Interaction Mapping, Protein Isoforms, Quantitative Trait Loci

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Nat Commun

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Springer Science and Business Media LLC
Wellcome Trust (107881/Z/15/Z)
MRC (1185)
Medical Research Council (MC_UU_00002/4)