Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-018-04931-0
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Funding
- BHF [CH/13/2/30154, RG/15/12/31616]
- BBSRC [BB/J004480/1]
- MRC [MC_UP_1302/5, MR/L007150/1]
- Wellcome Trust [097820/Z/11/A, WT107881]
- BHF 4-Year PhD Studentship Programme [FS/16/58/32734]
- University of Manchester PUHSC Alliance
- China Scholarships Council
- HEFCE
- Common Fund of the Office of the Director of the National Institutes of Health
- NCI
- NHGRI
- NHLBI
- NIDA
- NIMH
- NINDS
- BBSRC [BB/M022285/1, BBS/E/B/000C0422] Funding Source: UKRI
- MRC [MC_UU_00002/4, MC_EX_MR/S300002/1] Funding Source: UKRI
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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.
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