The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes

Tian-Peng Gu, Fan Guo, Hui Yang, Hai-Ping Wu, Gui-Fang Xu, Wei Liu, Zhi-Guo Xie, Linyu Shi, Xinyi He, Seung-gi Jin, Khursheed Iqbal, Yujiang Geno Shi, Zixin Deng, Piroska E. Szabó, Gerd P. Pfeifer, Jinsong Li () and Guo-Liang Xu ()
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Tian-Peng Gu: Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Fan Guo: Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Hui Yang: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Hai-Ping Wu: Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Gui-Fang Xu: Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Wei Liu: Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Zhi-Guo Xie: Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Linyu Shi: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Xinyi He: The State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiaotong University
Seung-gi Jin: Beckman Research Institute of the City of Hope
Khursheed Iqbal: Beckman Research Institute of the City of Hope
Yujiang Geno Shi: Diabetes, and Hypertension, Brigham and Women’s Hospital and Harvard Medical School
Zixin Deng: The State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiaotong University
Piroska E. Szabó: Beckman Research Institute of the City of Hope
Gerd P. Pfeifer: Beckman Research Institute of the City of Hope
Jinsong Li: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Guo-Liang Xu: Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

Nature, 2011, vol. 477, issue 7366, 606-610

Abstract: Oocyte reprogramming by Tet3 The paternal genome in a zygote undergoes active DNA demethylation before the fusion of the male and female pronuclei, and this coincides with oxidation of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Here, Gu et al. generate conditional knockout mice lacking catalytic activity of the dioxygenase Tet3. In Tet3-deficient zygotes, conversion of 5mC into 5hmC in the paternal genome fails to occur and the level of 5mC remains constant. The demethylation of paternal Oct4 and Nanog genes is also impeded. Therefore, Tet3-mediated 5mC oxidation contributes to demethylation and gene activation in the zygotic paternal genome.

Date: 2011
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DOI: 10.1038/nature10443

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