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UHRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells

Author

Listed:
  • Juan Dong

    (Huazhong University of Science and Technology)

  • Xiaoli Wang

    (Huazhong University of Science and Technology)

  • Congcong Cao

    (Huazhong University of Science and Technology)

  • Yujiao Wen

    (Huazhong University of Science and Technology)

  • Akihiko Sakashita

    (Cincinnati Children’s Hospital Medical Center)

  • Si Chen

    (Huazhong University of Science and Technology)

  • Jin Zhang

    (Huazhong University of Science and Technology
    Northwest A&F University)

  • Yue Zhang

    (Nanjing Medical University)

  • Liquan Zhou

    (Huazhong University of Science and Technology)

  • Mengcheng Luo

    (Wuhan University
    Hubei Provincial Key Laboratory of Developmentally Originated Disease)

  • Mingxi Liu

    (Nanjing Medical University)

  • Aihua Liao

    (Huazhong University of Science and Technology)

  • Satoshi H. Namekawa

    (Cincinnati Children’s Hospital Medical Center)

  • Shuiqiao Yuan

    (Huazhong University of Science and Technology
    Shenzhen Huazhong University of Science and Technology Research Institute)

Abstract

DNA methylation, repressive histone marks, and PIWI-interacting RNA (piRNA) are essential for the control of retrotransposon silencing in the mammalian germline. However, it remains unknown how these repressive epigenetic pathways crosstalk to ensure retrotransposon silencing in the male germline. Here, we show that UHRF1 is responsible for retrotransposon silencing and cooperates with repressive epigenetic pathways in male germ cells. Conditional loss of UHRF1 in postnatal germ cells causes DNA hypomethylation, upregulation of retrotransposons, the activation of a DNA damage response, and switches in the global chromatin status, leading to complete male sterility. Furthermore, we show that UHRF1 interacts with PRMT5, an arginine methyltransferase, to regulate the repressive histone arginine modifications (H4R3me2s and H3R2me2s), and cooperates with the PIWI pathway during spermatogenesis. Collectively, UHRF1 regulates retrotransposon silencing in male germ cells and provides a molecular link between DNA methylation, histone modification, and the PIWI pathway in the germline.

Suggested Citation

  • Juan Dong & Xiaoli Wang & Congcong Cao & Yujiao Wen & Akihiko Sakashita & Si Chen & Jin Zhang & Yue Zhang & Liquan Zhou & Mengcheng Luo & Mingxi Liu & Aihua Liao & Satoshi H. Namekawa & Shuiqiao Yuan, 2019. "UHRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12455-4
    DOI: 10.1038/s41467-019-12455-4
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    Cited by:

    1. Shenglei Feng & Jinmei Li & Hui Wen & Kuan Liu & Yiqian Gui & Yujiao Wen & Xiaoli Wang & Shuiqiao Yuan, 2022. "hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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