KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA-DNA triplexes and HP1 binding

doi:10.1038/s41556-022-01008-5

	KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA-DNA triplexes and HP1 binding
	Zhang, Xiaoli 1; Jiang, Quanlong 2,3; Li, Jiyang2,3,4 ; Zhang, Shiqiang 1,2,3; Cao, Yaqiang 2,3; Xia, Xian 5; Cai, Donghong 2,3; Tan, Jiaqi 1; Chen, Jiekai 6; Han, Jing-Dong J.1
	2022-10
发表期刊	NATURE CELL BIOLOGY (IF:17.3[JCR-2023],24.2[5-Year])
ISSN	1465-7392
EISSN	1476-4679
DOI	10.1038/s41556-022-01008-5
摘要	Transposon (de)repression and heterochromatin reorganization are dynamically regulated during cell fate determination and are hallmarks of cellular senescence. However, whether they are sequence specifically regulated remains unknown. Here we uncover that the KCNQ1OT1 lncRNA, by sequence-specific Hoogsteen base pairing with double-stranded genomic DNA via its repeat-rich region and binding to the heterochromatin protein HP1 alpha, guides, induces and maintains epigenetic silencing at specific repetitive DNA elements. Repressing KCNQ1OT1 or deleting its repeat-rich region reduces DNA methylation and H3K9me3 on KCNQ1OT1-targeted transposons. Engineering a fusion KCNQ1OT1 with an ectopically targeting guiding triplex sequence induces de novo DNA methylation at the target site. Phenotypically, repressing KCNQ1OT1 induces senescence-associated heterochromatin foci, transposon activation and retrotransposition as well as cellular senescence, demonstrating an essential role of KCNQ1OT1 to safeguard against genome instability and senescence.
收录类别	SCIE
语种	英语
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000870667400003
出版者	NATURE PORTFOLIO
原始文献类型	Article; Early Access
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243301
专题	生命科学与技术学院_博士生
通讯作者	Han, Jing-Dong J.
作者单位	1.Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Ctr Quantitat Biol CQB, Beijing, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci, CAS Key Lab Computat Biol, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Beijing, Peoples R China; 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 5.Nanjing Univ Chinese Med, Dept Pharmacol, Nanjing, Peoples R China; 6.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol, Guangzhou, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiaoli,Jiang, Quanlong,Li, Jiyang,et al. KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA-DNA triplexes and HP1 binding[J]. NATURE CELL BIOLOGY,2022.
APA	Zhang, Xiaoli.,Jiang, Quanlong.,Li, Jiyang.,Zhang, Shiqiang.,Cao, Yaqiang.,...&Han, Jing-Dong J..(2022).KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA-DNA triplexes and HP1 binding.NATURE CELL BIOLOGY.
MLA	Zhang, Xiaoli,et al."KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA-DNA triplexes and HP1 binding".NATURE CELL BIOLOGY (2022).