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

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

研究成果: Article査読

14 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号4705
ジャーナルNature communications
10
1
DOI
出版ステータスPublished - 2019 12 1
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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