PMID- 30478328 OWN - NLM STAT- MEDLINE VI - 9 IP - 1 TI - Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development. PG - 4977 LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Nat Commun JT - Nature communications JID - 101528555 IS - 2041-1723 (Electronic) LID - 10.1038/s41467-018-07451-z [doi] FAU - Yuan, Xuefei AU - Yuan X AD - Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. AD - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. AD - Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada. FAU - Song, Mengyi AU - Song M AD - Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. AD - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. AD - Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada. FAU - Devine, Patrick AU - Devine P AD - Gladstone Institutes, San Francisco, CA, 94158, USA. AD - Department of Pathology, University of California, San Francisco, San Francisco, CA, 94143-0511, USA. FAU - Bruneau, Benoit G AU - Bruneau BG AD - Gladstone Institutes, San Francisco, CA, 94158, USA. AD - Department of Pediatrics and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, 94158, USA. FAU - Scott, Ian C AU - Scott IC AD - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. ian.scott@sickkids.ca. AD - Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada. ian.scott@sickkids.ca. FAU - Wilson, Michael D AU - Wilson MD AUID- ORCID: http://orcid.org/0000-0002-4015-3066 AD - Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. michael.wilson@sickkids.ca. AD - Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada. michael.wilson@sickkids.ca. IS - 2041-1723 (Linking) RN - 0 (Chromatin) RN - 0 (DNA, Intergenic) SB - IM MH - Animals MH - Cell Lineage/genetics MH - Cell Separation MH - Chromatin/metabolism MH - Conserved Sequence/*genetics MH - DNA, Intergenic/genetics MH - *Embryonic Development MH - *Enhancer Elements, Genetic MH - *Gene Expression Regulation, Developmental MH - Heart/*embryology MH - Humans MH - Mice MH - Stem Cells/metabolism MH - Zebrafish/*embryology/*genetics PMC - PMC6255839 DCOM- 20181231 LR - 20191126 DP - 20181126 DEP - 20181126 AB - 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.