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

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

Yuan X1,2,3, Song M1,2,3, Devine P4,5, Bruneau BG4,6, Scott IC7,8, Wilson MD9,10.

Author information

1
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
2
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
3
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
4
Gladstone Institutes, San Francisco, CA, 94158, USA.
5
Department of Pathology, University of California, San Francisco, San Francisco, CA, 94143-0511, USA.
6
Department of Pediatrics and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, 94158, USA.
7
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. ian.scott@sickkids.ca.
8
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada. ian.scott@sickkids.ca.
9
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. michael.wilson@sickkids.ca.
10
Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada. michael.wilson@sickkids.ca.

Abstract

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.

PMID:
30478328
PMCID:
PMC6255839
DOI:
10.1038/s41467-018-07451-z
[Indexed for MEDLINE]
Free PMC Article

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