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

Choy, Mun-Kit ORCID: https://orcid.org/0000-0003-3998-0774, Javierre, Biola M, Williams, Simon G, Baross, Stephanie L, Liu, Yingjuan, Wingett, Steven W, Akbarov, Artur, Wallace, Chris, Freire-Pritchett, Paula, Rugg-Gunn, Peter J, Spivakov, Mikhail, Fraser, Peter and Keavney, Bernard D (2018) Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks. Nature Communications, 9 (1). 2526. ISSN 2041-1723

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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.