Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development

Nat Commun. 2018 Nov 26;9(1):4977. doi: 10.1038/s41467-018-07451-z.


During the phylotypic period, embryos from different genera show similar gene expression patterns, implying common regulatory mechanisms. Here we set out to identify enhancers involved in the initial events of cardiogenesis, which occurs during the phylotypic period. We isolate early cardiac progenitor cells from zebrafish embryos and characterize 3838 open chromatin regions specific to this cell population. Of these regions, 162 overlap with conserved non-coding elements (CNEs) that also map to open chromatin regions in human. Most of the zebrafish conserved open chromatin elements tested drive gene expression in the developing heart. Despite modest sequence identity, human orthologous open chromatin regions recapitulate the spatial temporal expression patterns of the zebrafish sequence, potentially providing a basis for phylotypic gene expression patterns. Genome-wide, we discover 5598 zebrafish-human conserved open chromatin regions, suggesting that a diverse repertoire of ancient enhancers is established prior to organogenesis and the phylotypic period.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Cell Separation
  • Chromatin / metabolism
  • Conserved Sequence / genetics*
  • DNA, Intergenic / genetics
  • Embryonic Development*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental*
  • Heart / embryology*
  • Humans
  • Mice
  • Stem Cells / metabolism
  • Zebrafish / embryology*
  • Zebrafish / genetics*


  • Chromatin
  • DNA, Intergenic