An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo.

ABSTRACT: Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia disorders. Here, we identify an evolutionary conserved regulatory cluster with super enhancer characteristics downstream of SCN5A, which drives localized cardiac expression and contains conduction velocity-associated variants. We use genome editing to create a series of deletions in the mouse genome and show that the enhancer cluster controls the conformation of a >0.5 Mb genomic region harboring multiple interacting gene promoters and enhancers. We find that this cluster and its individual components are selectively required for cardiac Scn5a expression, normal cardiac conduction and normal embryonic development. Our s

SUBMITTER: Man JCK 

PROVIDER: S-EPMC6821807 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature