On October 17, Prof. YUAN Shuiqiao of the Institute of Reproductive Health published his latest research paper in Nature Communications titled HRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells
The following is the abstract of Prof. Yuan's latest findins: 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.
Prof. Yuan's final results are: UHRF1 displays a dynamic nuclear-cytoplasmic expression
UHRF1 displays a dynamic expression profile during adult spermatogenesis. Double immunostaining with UHRF1 and γ-H2A.X on WT (wild-type) germ cells from adult testis sections are shown. Scale bar = 10 μm.bA schematic summary of the dynamic localizations of UHRF1 in adult testis during spermatogenesis. Note: the localization drawing based on the fluorescent signal analyses from five independent experiments. Spg, Spermatogonia; PL, Pre-leptotene; L, Leptotene; Z, Zygotene; EP, early pachytene; P, Pachytene; D, Diplotene; Rs, Round spermatids; Es, Elongating spermatids; S, Spermatozoa
The Institute of Reproductive Health has been introducing and supportingyoung and middle-aged talents for years. Professor YUAN Shuiqiao was sincerely invited to work here in 2016 as an overseas talent. After returning home, he established his own research team, set up a platform and actively committed to study the mechanism of male sterility. This is a big breakthrough afte his interpretation on the pathogenesis of male infertility on PNAS in January 2019.