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Rewiring of the epigenome and chromatin architecture by exogenously induced retinoic acid signaling during zebrafish embryonic development.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2024 Apr 24; Vol. 52 (7), pp. 3682-3701. - Publication Year :
- 2024
-
Abstract
- Retinoic acid (RA) is the ligand of RA receptors (RARs), transcription factors that bind to RA response elements. RA signaling is required for multiple processes during embryonic development, including body axis extension, hindbrain antero-posterior patterning and forelimb bud initiation. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling during in vivo embryonic development. Here, we stimulate the RA pathway by treating zebrafish embryos with all-trans-RA (atRA) and use a combination of RNA-seq, ATAC-seq, ChIP-seq and HiChIP to gain insight into the molecular mechanisms by which exogenously induced RA signaling controls gene expression. We find that RA signaling is involved in anterior/posterior patterning, central nervous system development, and the transition from pluripotency to differentiation. AtRA treatment also alters chromatin accessibility during early development and promotes chromatin binding of RARαa and the RA targets Hoxb1b, Meis2b and Sox3, which cooperate in central nervous system development. Finally, we show that exogenous RA induces a rewiring of chromatin architecture, with alterations in chromatin 3D interactions involving target genes. Altogether, our findings identify genome-wide targets of RA signaling and provide a molecular mechanism by which developmental signaling pathways regulate target gene expression by altering chromatin topology.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- Animals
Chromatin metabolism
Embryo, Nonmammalian metabolism
Embryo, Nonmammalian drug effects
Epigenome
Signal Transduction drug effects
Zebrafish genetics
Zebrafish embryology
Zebrafish Proteins genetics
Zebrafish Proteins metabolism
Embryonic Development genetics
Embryonic Development drug effects
Gene Expression Regulation, Developmental drug effects
Tretinoin pharmacology
Tretinoin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 52
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 38321954
- Full Text :
- https://doi.org/10.1093/nar/gkae065