PMID- 34723970 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20211214 IS - 1553-7404 (Electronic) IS - 1553-7390 (Print) IS - 1553-7390 (Linking) VI - 17 IP - 11 DP - 2021 Nov TI - Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. PG - e1009890 LID - 10.1371/journal.pgen.1009890 [doi] LID - e1009890 AB - In contrast to mammals, the zebrafish maintains its cardiomyocyte proliferation capacity throughout adulthood. However, neither the molecular mechanisms that orchestrate the proliferation of cardiomyocytes during developmental heart growth nor in the context of regeneration in the adult are sufficiently defined yet. We identified in a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen the recessive, embryonic-lethal zebrafish mutant baldrian (bal), which shows severely impaired developmental heart growth due to diminished cardiomyocyte proliferation. By positional cloning, we identified a missense mutation in the zebrafish histone deacetylase 1 (hdac1) gene leading to severe protein instability and the loss of Hdac1 function in vivo. Hdac1 inhibition significantly reduces cardiomyocyte proliferation, indicating a role of Hdac1 during developmental heart growth in zebrafish. To evaluate whether developmental and regenerative Hdac1-associated mechanisms of cardiomyocyte proliferation are conserved, we analyzed regenerative cardiomyocyte proliferation after Hdac1 inhibition at the wound border zone in cryoinjured adult zebrafish hearts and we found that Hdac1 is also essential to orchestrate regenerative cardiomyocyte proliferation in the adult vertebrate heart. In summary, our findings suggest an important and conserved role of Histone deacetylase 1 (Hdac1) in developmental and adult regenerative cardiomyocyte proliferation in the vertebrate heart. FAU - Buhler, Anja AU - Buhler A AUID- ORCID: 0000-0003-2927-2379 AD - Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany. FAU - Gahr, Bernd M AU - Gahr BM AUID- ORCID: 0000-0002-5755-6603 AD - Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany. FAU - Park, Deung-Dae AU - Park DD AUID- ORCID: 0000-0001-6265-4964 AD - Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany. FAU - Bertozzi, Alberto AU - Bertozzi A AUID- ORCID: 0000-0003-3091-1481 AD - Institute of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany. FAU - Boos, Alena AU - Boos A AD - Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany. FAU - Dalvoy, Mohankrishna AU - Dalvoy M AUID- ORCID: 0000-0003-4430-4893 AD - Institute of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany. FAU - Pott, Alexander AU - Pott A AD - Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany. AD - Department of Internal Medicine II, University of Ulm, Ulm, Germany. FAU - Oswald, Franz AU - Oswald F AD - Department of Internal Medicine I, University of Ulm, Ulm, Germany. FAU - Kovall, Rhett A AU - Kovall RA AUID- ORCID: 0000-0003-0520-1613 AD - Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America. FAU - Kuhn, Bernhard AU - Kuhn B AUID- ORCID: 0000-0002-1855-7072 AD - Department of Pediatrics, University of Pittsburgh, and Richard King Mellon Institute for Pediatric Research and Division of Pediatric Cardiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America. FAU - Weidinger, Gilbert AU - Weidinger G AUID- ORCID: 0000-0003-3599-6760 AD - Institute of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany. FAU - Rottbauer, Wolfgang AU - Rottbauer W AUID- ORCID: 0000-0003-4725-6217 AD - Department of Internal Medicine II, University of Ulm, Ulm, Germany. FAU - Just, Steffen AU - Just S AUID- ORCID: 0000-0001-7396-1281 AD - Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211101 PL - United States TA - PLoS Genet JT - PLoS genetics JID - 101239074 RN - 0 (Zebrafish Proteins) RN - EC 3.5.1.98 (HDAC1 protein, zebrafish) RN - EC 3.5.1.98 (Histone Deacetylase 1) SB - IM MH - Animals MH - Cell Proliferation MH - Heart/*physiology MH - Histone Deacetylase 1/*metabolism MH - Myocytes, Cardiac/*cytology MH - Regeneration/*physiology MH - Zebrafish/*embryology MH - Zebrafish Proteins/*metabolism PMC - PMC8584950 COIS- The authors have declared that no competing interests exist. EDAT- 2021/11/02 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/11/01 CRDT- 2021/11/01 16:45 PHST- 2020/11/11 00:00 [received] PHST- 2021/10/18 00:00 [accepted] PHST- 2021/11/11 00:00 [revised] PHST- 2021/11/02 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/11/01 16:45 [entrez] PHST- 2021/11/01 00:00 [pmc-release] AID - PGENETICS-D-20-01716 [pii] AID - 10.1371/journal.pgen.1009890 [doi] PST - epublish SO - PLoS Genet. 2021 Nov 1;17(11):e1009890. doi: 10.1371/journal.pgen.1009890. eCollection 2021 Nov.