Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA.
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Biol Reprod. 2021 Sep 14;105(3):603-612. doi: 10.1093/biolre/ioab086.
Previous studies have shown that Dnmt2-null sperm block the paternal transmission (through sperm) of certain acquired traits, e.g., high-fat diet-induced metabolic disorders or white tails due to a Kit paramutation. Here, we report that DNMT2 is also required for the transmission of a Kit paramutant phenotype (white tail tip) through the female germline (i.e., oocytes). Specifically, ablation of Dnmt2 led to aberrant profiles of tRNA-derived small RNAs (tsRNAs) and other small noncoding RNAs (sncRNAs) in sperm, which correlate with altered mRNA transcriptomes in pronuclear zygotes derived from wild-type oocytes carrying the Kit paramutation and a complete blockage of transmission of the paramutant phenotype through oocytes. Together, the present study suggests that both paternal and maternal transmissions of epigenetic phenotypes require intact DNMT2 functions in the male germline.
先前的研究表明，Dnmt2 缺失的精子阻止了某些获得性特征的父系传递（通过精子），例如高脂肪饮食引起的代谢紊乱或由于 Kit 突变引起的白色尾巴。在这里，我们报告说，DNMT2 也需要通过雌性生殖系（即卵母细胞）传递 Kit 突变表型（白色尾巴尖端）。具体来说，Dnmt2 的缺失导致精子中 tRNA 衍生的小 RNA（tsRNA）和其他小非编码 RNA（sncRNA）的异常谱，这与来自携带 Kit 突变的野生型卵母细胞的原核合子中的 mRNA 转录组的改变相关，并且完全阻止了突变表型通过卵母细胞的传递。综上所述，本研究表明，父本和母本的表观遗传表型传递都需要雄性生殖系中完整的 DNMT2 功能。
