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

Mun-Kit Choy (), Biola M. Javierre, Simon G. Williams, Stephanie L. Baross, Yingjuan Liu, Steven W. Wingett, Artur Akbarov, Chris Wallace, Paula Freire-Pritchett, Peter J. Rugg-Gunn, Mikhail Spivakov, Peter Fraser () and Bernard D. Keavney ()
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Mun-Kit Choy: The University of Manchester
Biola M. Javierre: The Babraham Institute
Simon G. Williams: The University of Manchester
Stephanie L. Baross: The University of Manchester
Yingjuan Liu: The University of Manchester
Steven W. Wingett: The Babraham Institute
Artur Akbarov: The University of Manchester
Chris Wallace: University of Cambridge
Paula Freire-Pritchett: The Babraham Institute
Peter J. Rugg-Gunn: The Babraham Institute
Mikhail Spivakov: The Babraham Institute
Peter Fraser: The Babraham Institute
Bernard D. Keavney: The University of Manchester

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04931-0

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