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

Autor: Mun-Kit Choy, Javierre, Biola M., Williams, Simon G., Baross, Stephanie L., Yingjuan Liu, Wingett, Steven W., Akbarov, Artur, Wallace, Chris, Freire-Pritchett, Paula, Rugg-Gunn, Peter J., Spivakov, Mikhail, Fraser, Peter, Keavney, Bernard D.
Zdroj: Nature Communications; 6/28/2018, Vol. 9 Issue 1, p1-10, 10p, 6 Graphs
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index