Histone deacetylases 1 and 2 silence cryptic transcription to promote mitochondrial function during cardiogenesis
Authors
Milstone, Zachary J.Saheera, Sherin
Bourke, Lauren
Shpilka, Tomer
Haynes, Cole M.
Trivedi, Chinmay M.
UMass Chan Affiliations
Graduate School of Biomedical SciencesLi-Weibo Institute for Rare Diseases Research
Department of Molecular, Cell, and Cancer Biology
Department of Medicine, Division of Cardiovascular Medicine
Document Type
Journal ArticlePublication Date
2020-04-10Keywords
Hdac1Hdac2
mitochondrial function
cardiogenesis
silencing
transcription
Amino Acids, Peptides, and Proteins
Biochemical Phenomena, Metabolism, and Nutrition
Biochemistry
Cell Biology
Developmental Biology
Genetics and Genomics
Metadata
Show full item recordAbstract
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.Source
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. Link to article on publisher's site
DOI
10.1126/sciadv.aax5150Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41449PubMed ID
32300642Related Resources
Rights
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).Distribution License
http://creativecommons.org/licenses/by-nc/4.0/ae974a485f413a2113503eed53cd6c53
10.1126/sciadv.aax5150
Scopus Count
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).