气候变化领域集成服务门户(CCPortal): Hinfp is a guardian of the somatic genome by repressing transposable elements

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DOI	10.1073/pnas.2100839118
	Hinfp is a guardian of the somatic genome by repressing transposable elements
	Nirala N.K.; Li Q.; Ghule P.N.; Chen H.-J.; Li R.; Zhu L.J.; Wang R.; Rice N.P.; Mao J.; Stein J.L.; Stein G.S.; van Wijnen A.J.; Ip Y.T.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:41
英文摘要	Germ cells possess the Piwi-interacting RNA pathway to repress transposable elements and maintain genome stability across generations. Transposable element mobilization in somatic cells does not affect future generations, but nonetheless can lead to pathological outcomes in host tissues. We show here that loss of function of the conserved zinc-finger transcription factor Hinfp causes dysregulation of many host genes and derepression of most transposable elements. There is also substantial DNA damage in somatic tissues of Drosophila after loss of Hinfp. Interference of transposable element mobilization by reverse-transcriptase inhibitors can suppress some of the DNA damage phenotypes. The key cell-autonomous target of Hinfp in this process is Histone1, which encodes linker histones essential for higher-order chromatin assembly. Transgenic expression of Hinfp or Histone1, but not Histone4 of core nucleosome, is sufficient to rescue the defects in repressing transposable elements and host genes. Loss of Hinfp enhances Ras-induced tissue growth and aging-related phenotypes. Therefore, Hinfp is a physiological regulator of Histone1-dependent silencing of most transposable elements, as well as many host genes, and serves as a venue for studying genome instability, cancer progression, neurodegeneration, and aging. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Drosophila; Genome stability; Hinfp; Somatic; Transposable elements
语种	英语
scopus关键词	histone H1; transcription factor; transcription factor Hinfp; unclassified drug; aging; Article; chromatin assembly and disassembly; controlled study; DNA damage; Drosophila; gene; gene function; gene loss; gene repression; genome; genomic instability; nonhuman; nucleosome; protein expression; tissue growth; transposon
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/238781
作者单位	Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United Kingdom; Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, United States; University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, VT 05405, United States; Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, United States; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, United States; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, United States
推荐引用方式 GB/T 7714	Nirala N.K.,Li Q.,Ghule P.N.,et al. Hinfp is a guardian of the somatic genome by repressing transposable elements[J],2021,118(41).
APA	Nirala N.K..,Li Q..,Ghule P.N..,Chen H.-J..,Li R..,...&Ip Y.T..(2021).Hinfp is a guardian of the somatic genome by repressing transposable elements.Proceedings of the National Academy of Sciences of the United States of America,118(41).
MLA	Nirala N.K.,et al."Hinfp is a guardian of the somatic genome by repressing transposable elements".Proceedings of the National Academy of Sciences of the United States of America 118.41(2021).