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DOI	10.1073/pnas.2025281118
	Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist
	Liu L.; Rodriguez-Mateo C.; Huang P.; Huang A.; Lieu A.; Mao M.; Chung M.; Yang S.; Yu K.; Charville G.W.; Gan Q.; Rando T.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:37
英文摘要	Skeletal muscle possesses remarkable regenerative ability because of the resident muscle stem cells (MuSCs). A prominent feature of quiescent MuSCs is a high content of heterochromatin. However, little is known about the mechanisms by which heterochromatin is maintained in MuSCs. By comparing gene-expression profiles from quiescent and activated MuSCs, we found that the mammalian Hairless (Hr) gene is expressed in quiescent MuSCs and rapidly down-regulated upon MuSC activation. Using a mouse model in which Hr can be specifically ablated in MuSCs, we demonstrate that Hr expression is critical for MuSC function and muscle regeneration. In MuSCs, loss of Hr results in reduced trimethylated Histone 3 Lysine 9 (H3K9me3) levels, reduced heterochromatin, increased susceptibility to genotoxic stress, and the accumulation of DNA damage. Deletion of Hr leads to an acceleration of the age-related decline in MuSC numbers. We have also demonstrated that despite the fact that Hr is homologous to a family of histone demethylases and binds to di- and trimethylated H3K9, the expression of Hr does not lead to H3K9 demethylation. In contrast, we show that the expression of Hr leads to the inhibition of the H3K9 demethylase Jmjd1a and an increase in H3K9 methylation. Taking these data together, our study has established that Hr is a H3K9 demethylase antagonist specifically expressed in quiescent MuSCs. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Aging; Heterochromatin; Muscle stem cells
语种	英语
scopus关键词	histone demethylase; histone H3; protein Jmjd1a; unclassified drug; histone; hr protein, mouse; transcription factor; animal cell; animal experiment; animal model; animal tissue; Article; binding affinity; bioaccumulation; cell aging; cell death; cell function; cell structure; controlled study; DNA damage; down regulation; enzyme activity; enzyme inhibition; gene; gene deletion; gene expression regulation; genetic susceptibility; genotoxic stress; Hairless gene; heterochromatin; histone methylation; homeostasis; mouse; muscle regeneration; muscle stem cell; nonhuman; physiological stress; upregulation; animal; cytology; gene silencing; genetics; hairless mouse; metabolism; methylation; physiology; skeletal muscle; stem cell; Animals; Gene Silencing; Heterochromatin; Histone Demethylases; Histones; Methylation; Mice; Mice, Hairless; Muscle, Skeletal; Stem Cells; Transcription Factors
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251021
作者单位	Paul F. Glenn Center for the Biology of Aging, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, United States; Neurology Service and Rehabilitation Research and Development Center of Excellence, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, United States
推荐引用方式 GB/T 7714	Liu L.,Rodriguez-Mateo C.,Huang P.,et al. Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist[J],2021,118(37).
APA	Liu L..,Rodriguez-Mateo C..,Huang P..,Huang A..,Lieu A..,...&Rando T.A..(2021).Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist.Proceedings of the National Academy of Sciences of the United States of America,118(37).
MLA	Liu L.,et al."Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist".Proceedings of the National Academy of Sciences of the United States of America 118.37(2021).