Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1
文献类型:期刊论文
作者 | Li, Yingfeng1,2,3; Zhang, Zhuqiang2; Li, Xiang2,3; Dong, Qiang2,3; Tan, Jiajun2; Zheng, Yong2; Zhu, Bing2,9; Xu, Shaohua3; Chen, Jiayu4; Liu, Wenqiang4 |
刊名 | NATURE |
出版日期 | 2018 |
卷号 | 564期号:7734页码:136-+ |
ISSN号 | 0028-0836 |
关键词 | Dna Methylation Methyltransferase Demethylation Cells Gene Electroporation Establishment Purification Expression Tet3 |
DOI | 10.1038/s41586-018-0751-5 |
文献子类 | Article |
英文摘要 | Postnatal growth of mammalian oocytes is accompanied by a progressive gain of DNA methylation, which is predominantly mediated by DNMT3A, a de novo DNA methyltransferase(1,2). Unlike the genome of sperm and most somatic cells, the oocyte genome is hypomethylated in transcriptionally inert regions(2-4). However, how such a unique feature of the oocyte methylome is determined and its contribution to the developmental competence of the early embryo remains largely unknown. Here we demonstrate the importance of Stella, a factor essential for female fertility(5-7), in shaping the oocyte methylome in mice. Oocytes that lack Stella acquire excessive DNA methylation at the genome-wide level, including in the promoters of inactive genes. Such aberrant hypermethylation is partially inherited by two-cell-stage embryos and impairs zygotic genome activation. Mechanistically, the loss of Stella leads to ectopic nuclear accumulation of the DNA methylation regulator UHRF1(8,9), which results in the mislocalization of maintenance DNA methyltransferase DNMT1 in the nucleus. Genetic analysis confirmed the primary role of UHRF1 and DNMT1 in generating the aberrant DNA methylome in Stella-deficient oocytes. Stella therefore safeguards the unique oocyte epigenome by preventing aberrant de novo DNA methylation mediated by DNMT1 and UHRF1. |
电子版国际标准刊号 | 1476-4687 |
WOS研究方向 | Multidisciplinary Sciences |
语种 | 英语 |
WOS记录号 | WOS:000452269400055 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3472] |
专题 | 生化所2018年发文 |
通讯作者 | Xu, Shaohua |
作者单位 | 1.Beijing Normal Univ, Coll Life Sci, Beijing, Peoples R China; 2.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing, Peoples R China; 3.Natl Inst Biol Sci, Beijing, Peoples R China; 4.Tongji Univ, Clin & Translat Res Ctr, Shanghai Matern & Infant Hosp 1, Shanghai Key Lab Signaling & Dis Res,Sch Life Sci, Shanghai, Peoples R China; 5.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing, Peoples R China; 6.Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA; 7.East China Normal Univ, Shanghai Key Lab Regulatory Biol, Fengxian Dist Cent Hosp, ECNU Joint Ctr Translat Med,Inst Biomed Sci, Shanghai, Peoples R China; 8.East China Normal Univ, Sch Life Sci, Shanghai, Peoples R China; 9.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China; 10.Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA; |
推荐引用方式 GB/T 7714 | Li, Yingfeng,Zhang, Zhuqiang,Li, Xiang,et al. Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1[J]. NATURE,2018,564(7734):136-+. |
APA | Li, Yingfeng.,Zhang, Zhuqiang.,Li, Xiang.,Dong, Qiang.,Tan, Jiajun.,...&Xu, Guo-Liang.(2018).Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1.NATURE,564(7734),136-+. |
MLA | Li, Yingfeng,et al."Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1".NATURE 564.7734(2018):136-+. |
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