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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

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

doi

10.1038/s41467-018-04931-0

subject

Has Abstract

pub_date

2018-06-28 00:00:00

pages

2526

issue

1

issn

2041-1723

pii

10.1038/s41467-018-04931-0

journal_volume

9

pub_type

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