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Identification of d...
Identification of downstream effectors of retinoic acid specifying the zebrafish pancreas by integrative genomics
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- López-Pérez, Ana R. (författare)
- Laboratory of Zebrafish Development and Disease Models (ZDDM), GIGA-R, SART TILMAN, University of Liège, Avenue de l’Hôpital 1, B34, Liège, Belgium
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- Balwierz, Piotr J. (författare)
- Institute of Clinical Sciences and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, United Kingdom
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- Lenhard, Boris (författare)
- Institute of Clinical Sciences and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London, United Kingdom
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- Muller, Ferenc (författare)
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
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- Wardle, Fiona C. (författare)
- Randall Centre for Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London, United Kingdom
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- Manfroid, Isabelle (författare)
- Laboratory of Zebrafish Development and Disease Models (ZDDM), GIGA-R, SART TILMAN, University of Liège, Avenue de l’Hôpital 1, B34, Liège, Belgium
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- Voz, Marianne L. (författare)
- Laboratory of Zebrafish Development and Disease Models (ZDDM), GIGA-R, SART TILMAN, University of Liège, Avenue de l’Hôpital 1, B34, Liège, Belgium
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- Peers, Bernard (författare)
- Laboratory of Zebrafish Development and Disease Models (ZDDM), GIGA-R, SART TILMAN, University of Liège, Avenue de l’Hôpital 1, B34, Liège, Belgium
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(creator_code:org_t)
- 2021-11-22
- 2021
- Engelska.
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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