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

Published version
Peer-reviewed

Type

Article

Change log

Authors

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

Abstract

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.

Description

Keywords

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

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

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