气候变化领域集成服务门户(CCPortal): The RHOX gene cluster suppresses germline LINE1 transposition

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DOI	10.1073/pnas.2024785118
	The RHOX gene cluster suppresses germline LINE1 transposition
	Tan K.; Kim M.E.; Song H.-W.; Skarbrevik D.; Babajanian E.; Bedrosian T.A.; Gage F.H.; Wilkinson M.F.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:23
英文摘要	Transposable elements (TEs) are mobile sequences that engender widespread mutations and thus are a major hazard that must be silenced. The most abundant active class of TEs in mammalian genomes is long interspersed element class 1 (LINE1). Here, we report that LINE1 transposition is suppressed in the male germline by transcription factors encoded by a rapidly evolving X-linked homeobox gene cluster. LINE1 transposition is repressed by many members of this RHOX transcription factor family, including those with different patterns of expression during spermatogenesis. One family member-RHOX10-suppresses LINE1 transposition during fetal development in vivo when the germline would otherwise be susceptible to LINE1 activation because of epigenetic reprogramming. We provide evidence that RHOX10 suppresses LINE transposition by inducing Piwil2, which encodes a key component in the Piwi-interacting RNA pathway that protects against TEs. The ability of RHOX transcription factors to suppress LINE1 is conserved in humans but is lost in RHOXF2 mutants from several infertile human patients, raising the possibility that loss of RHOXF2 causes human infertility by allowing uncontrolled LINE1 expression in the germline. Together, our results support a model in which the Rhox gene cluster is in an evolutionary arms race with TEs, resulting in expansion of the Rhox gene cluster to suppress TEs in different biological contexts. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	LINE1; PiRNA; Piwil2; RHOX10; Transposon
语种	英语
scopus关键词	Piwi interacting RNA; transcription factor; transcription factor RHOX; transcription factor RHOX10; unclassified drug; homeodomain protein; RHOXF2 protein, human; transcription factor; adult; animal experiment; animal tissue; Article; controlled study; DNA transposition; epigenetics; gene; gene cluster; gene expression profiling; gene loss; gene repression; germ line; homeobox; human; human cell; human tissue; long interspersed nuclear element 1; male; male infertility; mouse; nonhuman; Piwil2 gene; Rhox gene; RHOXF2 gene; spermatogenesis; animal; C57BL mouse; gene expression regulation; genetics; germ cell; HEK293 cell line; long interspersed nuclear element; metabolism; multigene family; physiology; transposon; X chromosomal inheritance; Animals; DNA Transposable Elements; Gene Expression Regulation; Genes, X-Linked; Germ Cells; HEK293 Cells; Homeodomain Proteins; Humans; Long Interspersed Nucleotide Elements; Male; Mice; Mice, Inbred C57BL; Multigene Family; Spermatogenesis; 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/251156
作者单位	Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California San Diego, San Diego, CA 92093, United States; Laboratory of Genetics, The Salk Institute for Biological Studies, San Diego, CA 92037, United States; Institute of Genomic Medicine, University of California San Diego, San Diego, CA 92093, United States
推荐引用方式 GB/T 7714	Tan K.,Kim M.E.,Song H.-W.,et al. The RHOX gene cluster suppresses germline LINE1 transposition[J],2021,118(23).
APA	Tan K..,Kim M.E..,Song H.-W..,Skarbrevik D..,Babajanian E..,...&Wilkinson M.F..(2021).The RHOX gene cluster suppresses germline LINE1 transposition.Proceedings of the National Academy of Sciences of the United States of America,118(23).
MLA	Tan K.,et al."The RHOX gene cluster suppresses germline LINE1 transposition".Proceedings of the National Academy of Sciences of the United States of America 118.23(2021).