Chamber-specific chromatin architecture guides functional interpretation of disease-associated Cis-regulatory elements in human cardiomyocytes.

ABSTRACT: Cis-regulatory elements (CREs) are noncoding DNA regions regulating cell-type-specific gene expression programs by interacting with distal gene promoters. Here, we aim to decode the function and spatial organization of CRE-promoter interactions in human cardiomyocytes. We analyzed the epigenome and chromatin interactions of human male atrial, ventricular, and failing cardiomyocytes. Atrial and ventricular cardiomyocytes harbored chamber-specific CRE-promoter interactions modulating gene expression as confirmed by functional epigenetic silencing. These CRE-promoter interactions explain the distinct contribution of non-coding genetic variants to atrial and ventricular diseases, such as dilated cardiomyopathy and arrhythmias. We dissected the prototypic KCNJ2 locus, encoding a potassium chann

SUBMITTER: Haydar S 

PROVIDER: S-EPMC12796357 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature