Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1

Yingfeng Li, Zhuqiang Zhang, Jiayu Chen, Wenqiang Liu, Weiyi Lai, Baodong Liu, Xiang Li, Liping Liu, Shaohua Xu, Qiang Dong, Mingzhu Wang, Xiaoya Duan, Jiajun Tan, Yong Zheng, Pumin Zhang, Guoping Fan, Jiemin Wong, Guo-Liang Xu, Zhigao Wang, Hailin Wang, Shaorong Gao and Bing Zhu ()
Additional contact information
Yingfeng Li: Beijing Normal University
Zhuqiang Zhang: Institute of Biophysics, Chinese Academy of Sciences
Jiayu Chen: Tongji University
Wenqiang Liu: Tongji University
Weiyi Lai: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences
Baodong Liu: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences
Xiang Li: Institute of Biophysics, Chinese Academy of Sciences
Liping Liu: University of Texas Southwestern Medical Center
Shaohua Xu: National Institute of Biological Sciences
Qiang Dong: Institute of Biophysics, Chinese Academy of Sciences
Mingzhu Wang: Tongji University
Xiaoya Duan: Institute of Biomedical Sciences and School of Life Sciences, East China Normal University
Jiajun Tan: Institute of Biophysics, Chinese Academy of Sciences
Yong Zheng: Institute of Biophysics, Chinese Academy of Sciences
Pumin Zhang: Baylor College of Medicine
Guoping Fan: David Geffen School of Medicine, University of California, Los Angeles
Jiemin Wong: Institute of Biomedical Sciences and School of Life Sciences, East China Normal University
Guo-Liang Xu: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Zhigao Wang: University of Texas Southwestern Medical Center
Hailin Wang: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences
Shaorong Gao: Tongji University
Bing Zhu: Institute of Biophysics, Chinese Academy of Sciences

Nature, 2018, vol. 564, issue 7734, 136-140

Abstract: Abstract Postnatal growth of mammalian oocytes is accompanied by a progressive gain of DNA methylation, which is predominantly mediated by DNMT3A, a de novo DNA methyltransferase1,2. Unlike the genome of sperm and most somatic cells, the oocyte genome is hypomethylated in transcriptionally inert regions2–4. 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 fertility5–7, 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 UHRF18,9, 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.

Keywords: Oocyte Genome; Major Satellite Repeats; Bisulfite Sanger Sequencing; Spindle-chromosome Complex; Media Assets (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (8)

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DOI: 10.1038/s41586-018-0751-5

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