Format

Send to

Choose Destination
Nat Commun. 2018 Jun 28;9(1):2526. doi: 10.1038/s41467-018-04931-0.

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

Author information

1
Division of Cardiovascular Sciences, The University of Manchester, Manchester, M13 9PT, UK. munkit.choy@manchester.ac.uk.
2
Nuclear Dynamics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.
3
Josep Carreras Leukaemia Research Institute, Campus ICO-Germans Trias I Pujol, Badalona, 08916, Barcelona, Spain.
4
Division of Cardiovascular Sciences, The University of Manchester, Manchester, M13 9PT, UK.
5
MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK.
6
Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
7
Division of Cell Biology, Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
8
Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.
9
Nuclear Dynamics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK. pfraser@bio.fsu.edu.
10
Department of Biological Science, Florida State University, Tallahassee, 32306, FL, USA. pfraser@bio.fsu.edu.
11
Division of Cardiovascular Sciences, The University of Manchester, Manchester, M13 9PT, UK. bernard.keavney@manchester.ac.uk.

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.

PMID:
29955040
PMCID:
PMC6023870
DOI:
10.1038/s41467-018-04931-0
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center