TY - JOUR
T1 - UHRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells
AU - Dong, Juan
AU - Wang, Xiaoli
AU - Cao, Congcong
AU - Wen, Yujiao
AU - Sakashita, Akihiko
AU - Chen, Si
AU - Zhang, Jin
AU - Zhang, Yue
AU - Zhou, Liquan
AU - Luo, Mengcheng
AU - Liu, Mingxi
AU - Liao, Aihua
AU - Namekawa, Satoshi H.
AU - Yuan, Shuiqiao
N1 - Funding Information:
We thank Dr. Wei Yan at University of Nevada, Reno for discussion and helpful comments regarding the paper. This work supported by grants from National Natural Science Foundation of China (31671551 to S.Y.), the Science Technology and Innovation Commission of Shenzhen Municipality (JCYJ20170244 to S.Y.), Natural Science Foundation of Hubei Province (2017CFA069 to S.Y.), and National Institute of Health R01 grants (GM098605 and GM122776 to S.H.N.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-12455-4
DO - 10.1038/s41467-019-12455-4
M3 - Article
C2 - 31624244
AN - SCOPUS:85073538106
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4705
ER -