PUBLICATION

Rewiring of the epigenome and chromatin architecture by exogenously induced retinoic acid signaling during zebrafish embryonic development

Authors
Moreno-Oñate, M., Gallardo-Fuentes, L., Martínez-García, P.M., Naranjo, S., Jiménez-Gancedo, S., Tena, J.J., Santos-Pereira, J.M.
ID
ZDB-PUB-240207-9
Date
2024
Source
Nucleic acids research   52(7): 3682-3701 (Journal)
Registered Authors
Naranjo, Silvia, Tena, Juan
Keywords
none
Datasets
GEO:GSE233698
MeSH Terms
  • Animals
  • Chromatin/metabolism
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development*/drug effects
  • Embryonic Development*/genetics
  • Epigenome
  • Gene Expression Regulation, Developmental*/drug effects
  • Signal Transduction/drug effects
  • Tretinoin*/metabolism
  • Tretinoin*/pharmacology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
38321954 Full text @ Nucleic Acids Res.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping