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dc.contributor.authorMilstone, Zachary J.
dc.contributor.authorSaheera, Sherin
dc.contributor.authorBourke, Lauren
dc.contributor.authorShpilka, Tomer
dc.contributor.authorHaynes, Cole M
dc.contributor.authorTrivedi, Chinmay M.
dc.date2022-08-11T08:09:56.000
dc.date.accessioned2022-08-23T16:49:22Z
dc.date.available2022-08-23T16:49:22Z
dc.date.issued2020-04-10
dc.date.submitted2020-05-14
dc.identifier.citation<p>Milstone ZJ, Saheera S, Bourke LM, Shpilka T, Haynes CM, Trivedi CM. Histone deacetylases 1 and 2 silence cryptic transcription to promote mitochondrial function during cardiogenesis. Sci Adv. 2020 Apr 10;6(15):eaax5150. doi: 10.1126/sciadv.aax5150. PMID: 32300642; PMCID: PMC7148095. <a href="https://doi.org/10.1126/sciadv.aax5150">Link to article on publisher's site</a></p>
dc.identifier.issn2375-2548 (Linking)
dc.identifier.doi10.1126/sciadv.aax5150
dc.identifier.pmid32300642
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41449
dc.description.abstractCryptic transcription occurs widely across the eukaryotic genome; however, its regulation during vertebrate development is not understood. Here, we show that two class I histone deacetylases, Hdac1 and Hdac2, silence cryptic transcription to promote mitochondrial function in developing murine hearts. Mice lacking Hdac1 and Hdac2 in heart exhibit defective developmental switch from anaerobic to mitochondrial oxidative phosphorylation (OXPHOS), severe defects in mitochondrial mass, mitochondrial function, and complete embryonic lethality. Hdac1/Hdac2 promotes the transition to OXPHOS by enforcing transcriptional fidelity of metabolic gene programs. Mechanistically, Hdac1/Hdac2 deacetylates histone residues including H3K23, H3K14, and H4K16 to suppress cryptic transcriptional initiation within the coding regions of actively transcribed metabolic genes. Thus, Hdac1/2-mediated epigenetic silencing of cryptic transcription is essential for mitochondrial function during early vertebrate development.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32300642&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectHdac1
dc.subjectHdac2
dc.subjectmitochondrial function
dc.subjectcardiogenesis
dc.subjectsilencing
dc.subjecttranscription
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectGenetics and Genomics
dc.titleHistone deacetylases 1 and 2 silence cryptic transcription to promote mitochondrial function during cardiogenesis
dc.typeJournal Article
dc.source.journaltitleScience advances
dc.source.volume6
dc.source.issue15
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5248&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4229
dc.identifier.contextkey17740870
refterms.dateFOA2022-08-23T16:49:23Z
html.description.abstract<p>Cryptic transcription occurs widely across the eukaryotic genome; however, its regulation during vertebrate development is not understood. Here, we show that two class I histone deacetylases, Hdac1 and Hdac2, silence cryptic transcription to promote mitochondrial function in developing murine hearts. Mice lacking Hdac1 and Hdac2 in heart exhibit defective developmental switch from anaerobic to mitochondrial oxidative phosphorylation (OXPHOS), severe defects in mitochondrial mass, mitochondrial function, and complete embryonic lethality. Hdac1/Hdac2 promotes the transition to OXPHOS by enforcing transcriptional fidelity of metabolic gene programs. Mechanistically, Hdac1/Hdac2 deacetylates histone residues including H3K23, H3K14, and H4K16 to suppress cryptic transcriptional initiation within the coding regions of actively transcribed metabolic genes. Thus, Hdac1/2-mediated epigenetic silencing of cryptic transcription is essential for mitochondrial function during early vertebrate development.</p>
dc.identifier.submissionpathoapubs/4229
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentLi-Weibo Institute for Rare Diseases Research
dc.contributor.departmentDepartment of Molecular, Cell, and Cancer Biology
dc.contributor.departmentDepartment of Medicine, Division of Cardiovascular Medicine
dc.source.pageseaax5150


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Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Except where otherwise noted, this item's license is described as Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).