Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks.
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Choy, M., Javierre, B. M., Williams, S. G., Baross, S. L., Liu, Y., Wingett, S. W., Akbarov, A., et al. (2018). Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks.. Nature communications, 9 (1), 2526. https://doi.org/10.1038/s41467-018-04931-0
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.
Heart Conduction System, Heart Ventricles, Cell Line, Myocytes, Cardiac, Humans, Calpain, Actinin, Histones, Protein Isoforms, Protein Interaction Mapping, Cell Differentiation, Heart Rate, Quantitative Trait Loci, Genome, Human, Gene Regulatory Networks, Enhancer Elements, Genetic, Promoter Regions, Genetic, Genome-Wide Association Study, Human Embryonic Stem Cells
WELLCOME TRUST (107881/Z/15/Z)
Medical Research Council (MC_UU_00002/4)
External DOI: https://doi.org/10.1038/s41467-018-04931-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279777
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/