PUBLICATION

Identification of downstream effectors of retinoic acid specifying the zebrafish pancreas by integrative genomics

Authors
López-Pérez, A.R., Balwierz, P.J., Lenhard, B., Muller, F., Wardle, F.C., Manfroid, I., Voz, M.L., Peers, B.
ID
ZDB-PUB-211129-4
Date
2021
Source
Scientific Reports   11: 22717 (Journal)
Registered Authors
Manfroid, Isabelle, Peers, Bernard, Voz, Marianne, Wardle, Fiona
Keywords
none
Datasets
GEO:GSE168966, GEO:GSE168969, GEO:GSE168960, GEO:GSE168962
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation Sequencing
  • GATA Transcription Factors/genetics
  • GATA Transcription Factors/metabolism
  • Gene Expression Regulation, Developmental
  • Genomics*
  • Hepatocyte Nuclear Factor 1-beta/genetics
  • Hepatocyte Nuclear Factor 1-beta/metabolism
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Mice
  • Pancreas/drug effects*
  • Pancreas/embryology
  • Pancreas/metabolism
  • RNA-Seq
  • Receptors, Retinoic Acid/agonists*
  • Receptors, Retinoic Acid/genetics
  • Receptors, Retinoic Acid/metabolism
  • Signal Transduction
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transcriptome*
  • Tretinoin/pharmacology*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
34811400 Full text @ Sci. Rep.
Abstract
Retinoic acid (RA) is a key signal for the specification of the pancreas. Still, the gene regulatory cascade triggered by RA in the endoderm remains poorly characterized. In this study, we investigated this regulatory network in zebrafish by combining RNA-seq, RAR ChIP-seq and ATAC-seq assays. By analysing the effect of RA and of the RA receptor (RAR) inverse-agonist BMS493 on the transcriptome and on the chromatin accessibility of endodermal cells, we identified a large set of genes and regulatory regions regulated by RA signalling. RAR ChIP-seq further defined the direct RAR target genes in zebrafish, including hox genes as well as several pancreatic regulators like mnx1, insm1b, hnf1ba and gata6. Comparison of zebrafish and murine RAR ChIP-seq data highlighted the conserved direct target genes and revealed that some RAR sites are under strong evolutionary constraints. Among them, a novel highly conserved RAR-induced enhancer was identified downstream of the HoxB locus and driving expression in the nervous system and in the gut in a RA-dependent manner. Finally, ATAC-seq data unveiled the role of the RAR-direct targets Hnf1ba and Gata6 in opening chromatin at many regulatory loci upon RA treatment.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping