The heart is a heterocellular organ consisting of several cell types including cardiomyocytes. Cell-type specific gene expression and response to stimuli is modulated by active distal regulatory elements termed enhancers. Cardiac enhancers are enriched for disease-associated variants and spatially interact with distal target promoters. However, enhancer-promoter interactions and spatial chromatin organization of human adult cardiac myocytes have not been analyzed so far limiting the interpretation of disease-associated regulatory elements in these cells. Here we generated high resolution spatial chromatin interaction data for atrial, left ventricular and failing human adult cardiac myocytes and identified cell-type specific interaction signatures. An integrative analysis with comprehensive epigenetic data reveals cardiac myocyte-specific, chamber-specific and disease-relevant enhancer-promoter interactions in cardiac myocytes. We further identified the cardiac disease risk association of promoter-interacting versus non-interacting enhancers and experimentally proofed the functional importance of enhancers harboring long QT risk loci. Our data shows that decoding cell type-specific regulatory elements and their interacting promoters provides insights into regulatory mechanisms essential for cell function and genetic risk factors as demonstrated here for human cardiac myocytes. This data will facilitate the interpretation of non-coding genetic risk factors in future genome-wide association studies. These data will allow predicting whether non-coding genetic variants promote disease in adult cardiac myocytes or not.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.