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HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development

Coordinated transcriptional and epigenetic mechanisms that direct development of the later differentiating second heart field (SHF) progenitors remain largely unknown. Here, we show that a novel zebrafish histone deacetylase 1 (hdac1) mutant allele cardiac really gone (crg) has a deficit of ventricu...

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Autores principales: Song, Yuntao Charlie, Dohn, Tracy E., Rydeen, Ariel B., Nechiporuk, Alex V., Waxman, Joshua S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538190/
https://www.ncbi.nlm.nih.gov/pubmed/31091225
http://dx.doi.org/10.1371/journal.pgen.1008165
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author Song, Yuntao Charlie
Dohn, Tracy E.
Rydeen, Ariel B.
Nechiporuk, Alex V.
Waxman, Joshua S.
author_facet Song, Yuntao Charlie
Dohn, Tracy E.
Rydeen, Ariel B.
Nechiporuk, Alex V.
Waxman, Joshua S.
author_sort Song, Yuntao Charlie
collection PubMed
description Coordinated transcriptional and epigenetic mechanisms that direct development of the later differentiating second heart field (SHF) progenitors remain largely unknown. Here, we show that a novel zebrafish histone deacetylase 1 (hdac1) mutant allele cardiac really gone (crg) has a deficit of ventricular cardiomyocytes (VCs) and smooth muscle within the outflow tract (OFT) due to both cell and non-cell autonomous loss in SHF progenitor proliferation. Cyp26-deficient embryos, which have increased retinoic acid (RA) levels, have similar defects in SHF-derived OFT development. We found that nkx2.5(+) progenitors from Hdac1 and Cyp26-deficient embryos have ectopic expression of ripply3, a transcriptional co-repressor of T-box transcription factors that is normally restricted to the posterior pharyngeal endoderm. Furthermore, the ripply3 expression domain is expanded anteriorly into the posterior nkx2.5(+) progenitor domain in crg mutants. Importantly, excess ripply3 is sufficient to repress VC development, while genetic depletion of Ripply3 and Tbx1 in crg mutants can partially restore VC number. We find that the epigenetic signature at RA response elements (RAREs) that can associate with Hdac1 and RA receptors (RARs) becomes indicative of transcriptional activation in crg mutants. Our study highlights that transcriptional repression via the epigenetic regulator Hdac1 facilitates OFT development through directly preventing expression of the RA-responsive gene ripply3 within SHF progenitors.
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spelling pubmed-65381902019-06-05 HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development Song, Yuntao Charlie Dohn, Tracy E. Rydeen, Ariel B. Nechiporuk, Alex V. Waxman, Joshua S. PLoS Genet Research Article Coordinated transcriptional and epigenetic mechanisms that direct development of the later differentiating second heart field (SHF) progenitors remain largely unknown. Here, we show that a novel zebrafish histone deacetylase 1 (hdac1) mutant allele cardiac really gone (crg) has a deficit of ventricular cardiomyocytes (VCs) and smooth muscle within the outflow tract (OFT) due to both cell and non-cell autonomous loss in SHF progenitor proliferation. Cyp26-deficient embryos, which have increased retinoic acid (RA) levels, have similar defects in SHF-derived OFT development. We found that nkx2.5(+) progenitors from Hdac1 and Cyp26-deficient embryos have ectopic expression of ripply3, a transcriptional co-repressor of T-box transcription factors that is normally restricted to the posterior pharyngeal endoderm. Furthermore, the ripply3 expression domain is expanded anteriorly into the posterior nkx2.5(+) progenitor domain in crg mutants. Importantly, excess ripply3 is sufficient to repress VC development, while genetic depletion of Ripply3 and Tbx1 in crg mutants can partially restore VC number. We find that the epigenetic signature at RA response elements (RAREs) that can associate with Hdac1 and RA receptors (RARs) becomes indicative of transcriptional activation in crg mutants. Our study highlights that transcriptional repression via the epigenetic regulator Hdac1 facilitates OFT development through directly preventing expression of the RA-responsive gene ripply3 within SHF progenitors. Public Library of Science 2019-05-15 /pmc/articles/PMC6538190/ /pubmed/31091225 http://dx.doi.org/10.1371/journal.pgen.1008165 Text en © 2019 Song et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Song, Yuntao Charlie
Dohn, Tracy E.
Rydeen, Ariel B.
Nechiporuk, Alex V.
Waxman, Joshua S.
HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development
title HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development
title_full HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development
title_fullStr HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development
title_full_unstemmed HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development
title_short HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development
title_sort hdac1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538190/
https://www.ncbi.nlm.nih.gov/pubmed/31091225
http://dx.doi.org/10.1371/journal.pgen.1008165
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