Skip to main content
eScholarship
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate.

  • Author(s): Gao, Rui
  • Liang, Xingqun
  • Cheedipudi, Sirisha
  • Cordero, Julio
  • Jiang, Xue
  • Zhang, Qingquan
  • Caputo, Luca
  • Günther, Stefan
  • Kuenne, Carsten
  • Ren, Yonggang
  • Bhattacharya, Shoumo
  • Yuan, Xuejun
  • Barreto, Guillermo
  • Chen, Yihan
  • Braun, Thomas
  • Evans, Sylvia M
  • Sun, Yunfu
  • Dobreva, Gergana
  • et al.
Abstract

Generation of widely differing and specialized cell types from a single totipotent zygote involves large-scale transcriptional changes and chromatin reorganization. Pioneer transcription factors play key roles in programming the epigenome and facilitating recruitment of additional regulatory factors during successive cell lineage specification and differentiation steps. Here we show that Isl1 acts as a pioneer factor driving cardiomyocyte lineage commitment by shaping the chromatin landscape of cardiac progenitor cells. Using an Isl1 hypomorphic mouse line which shows congenital heart defects, genome-wide profiling of Isl1 binding together with RNA- and ATAC-sequencing of cardiac progenitor cells and their derivatives, we uncover a regulatory network downstream of Isl1 that orchestrates cardiogenesis. Mechanistically, we show that Isl1 binds to compacted chromatin and works in concert with the Brg1-Baf60c-based SWI/SNF complex to promote permissive cardiac lineage-specific alterations in the chromatin landscape not only of genes with critical functions in cardiac progenitor cells, but also of cardiomyocyte structural genes that are highly expressed when Isl1 itself is no longer present. Thus, the Isl1/Brg1-Baf60c complex plays a crucial role in orchestrating proper cardiogenesis and in establishing epigenetic memory of cardiomyocyte fate commitment.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View