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 Communjournal_title
Nature communicationsauthors
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 BDdoi
10.1038/s41467-018-04931-0subject
Has Abstractpub_date
2018-06-28 00:00:00pages
2526issue
1issn
2041-1723pii
10.1038/s41467-018-04931-0journal_volume
9pub_type
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