中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing

文献类型:期刊论文

作者Dong, Qiang1,2,3,4; Li, Xiang1,2,3,4; Wang, Cheng-Zhi3; Xu, Shaohua4; Yuan, Gang4; Shao, Wei4; Liu, Baodong5; Zheng, Yong3; Wang, Hailin; Lei, Xiaoguang4,6,7
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2018-04-24
卷号115期号:17页码:E4013-E4022
关键词Cse1l Dna Methylation Gene Silencing Nuclear Import Pathway
ISSN号0027-8424
DOI10.1073/pnas.1800505115
英文摘要Epigenetic silencing can be mediated by various mechanisms, and many regulators remain to be identified. Here, we report a genome-wide siRNA screening to identify regulators essential for maintaining gene repression of a CMV promoter silenced by DNA methylation. We identified CSE1L (chromosome segregation 1 like) as an essential factor for the silencing of the reporter gene and many endogenous methylated genes. CSE1L depletion did not cause DNA demethylation. On the other hand, the methylated genes derepressed by CSE1L depletion largely overlapped with methylated genes that were also reactivated by treatment with histone deacetylase inhibitors (HDACi). Gene silencing defects observed upon CSE1L depletion were linked to its nuclear import function for certain protein cargos because depletion of other factors involved in the same nuclear import pathway, including KPNAs and KPNB1 proteins, displayed similar derepression profiles at the genome-wide level. Therefore, CSE1L appears to be critical for the nuclear import of certain key repressive proteins. Indeed, NOVA1, HDAC1, HDAC2, and HDAC8, genes known as silencing factors, became delocalized into cytosol upon CSE1L depletion. This study suggests that the cargo specificity of the protein nuclear import system may impact the selectivity of gene silencing.
语种英语
WOS记录号WOS:000430697500021
出版者NATL ACAD SCIENCES
源URL[http://ir.iccas.ac.cn/handle/121111/43137]  
专题中国科学院化学研究所
通讯作者Zhang, Zhuqiang; Zhu, Bing
作者单位1.Peking Union Med Coll, Grad Program, Beijing 100730, Peoples R China
2.Chinese Acad Med Sci, Beijing 100730, Peoples R China
3.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China
4.Natl Inst Biol Sci, Beijing 102206, Peoples R China
5.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China
6.Peking Univ, Beijing Natl Lab Mol Sci, Dept Biol Chem, Coll Chem & Mol Engn, Beijing 100871, Peoples R China
7.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
8.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714
Dong, Qiang,Li, Xiang,Wang, Cheng-Zhi,et al. Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2018,115(17):E4013-E4022.
APA Dong, Qiang.,Li, Xiang.,Wang, Cheng-Zhi.,Xu, Shaohua.,Yuan, Gang.,...&Zhu, Bing.(2018).Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,115(17),E4013-E4022.
MLA Dong, Qiang,et al."Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 115.17(2018):E4013-E4022.

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来源:化学研究所

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