Hand2 Selectively Reorganizes Chromatin Accessibility to Induce Pacemaker-like Transcriptional Reprogramming

Antonio Fernandez-Perez, Adwait Amod Sathe, Minoti Bhakta, Kayla Leggett, Chao Xing, Nikhil Vilas Munshi

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Gata4, Hand2, Mef2c, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here, we explore the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and the endogenous sinoatrial node (SAN), yet key regulatory networks remain missing. We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression. Moreover, we identify a Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N terminus. By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation. Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.

Original languageEnglish (US)
Pages (from-to)2354-2369.e7
JournalCell Reports
Issue number8
StatePublished - May 21 2019


  • chromatin accessibility
  • desmosome
  • gene expression
  • pacemaker
  • reprogramming
  • transcriptome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Hand2 Selectively Reorganizes Chromatin Accessibility to Induce Pacemaker-like Transcriptional Reprogramming'. Together they form a unique fingerprint.

Cite this