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EP News: Basic and Translational

  • Nipavan Chiamvimonvat
    Correspondence
    Address reprint requests and correspondence: Dr Nipavan Chiamvimonvat, Department of Internal Medicine and Pharmacology, University of California, Davis, GBSF 6315, 451 Health Science Dr, Davis, CA 95616.
    Affiliations
    Department of Internal Medicine and Pharmacology, University of California, Davis, Davis, California
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Published:December 04, 2020DOI:https://doi.org/10.1016/j.hrthm.2020.12.002
      Galang et al (Circ Res 2020;127:1502, PMID 33044128) tested the epigenetic profile of cardiac pacemaker cells (PCs) using comparative ATAC-seq on the sorted neonatal mouse sinoatrial node (SAN) as compared with right atrial cardiomyocytes. PC-enriched ATAC-seq peaks, representing candidate SAN regulatory elements, were located near established SAN genes and were enriched for distinct sets of transcription factor binding sites. The authors identified a 2.9-kb regulatory element at the Isl1 locus that was active specifically in the cardiac inflow at E8.5 and throughout later SAN development and maturation. Deletion of this enhancer from the genome of mice resulted in SAN hypoplasia and sinus arrhythmias. Importantly, single nucleotide polymorphisms in the human genome, near the region syntenic to the mouse enhancer, exhibited a significant association with resting heart rate in human populations. The authors conclude that PCs exhibit distinct regions of accessible chromatin that correlate with their gene expression profile and contain novel SAN enhancers. Additionally, cis-regulation of Isl1 specifically in the SAN depends on a conserved SAN enhancer that regulates PC development and SAN function.
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