UHRF1 repressed 5’-hydroxymethylcytosine is essential for the male meiotic 1 prophase I
UHRF1 repressed 5’-hydroxymethylcytosine is essential for the male meiotic 1 prophase I
复制标题
UHRF1 抑制的 5-羟甲基胞嘧啶对于雄性减数分裂 1 前期 I 至关重要
作者：
Hongjie Pan;Ning Jiang;Shenfei Sun;Hanwei Jiang;Jianze Xu;Xiaohua Jiang;Qian Gao;Liang Li;Haili Wu;Huajun Zheng;Qi Qi;Tianqi Li;Meixing Zhang;Lingling Zhang;Xiaofeng Wan;Xinhua Lin;Jiemin Wong;Qinghua Shi;Runsheng Li
5’-羟甲基胞嘧啶 (5hmC) 是一种重要的 5’-胞嘧啶修饰，在雄性减数分裂前期顺序发生了高度改变。然而，这种动态变化的调节机制以及 5hmC 在减数分裂中的功能仍然很大程度上未知。使用基因敲除小鼠模型，我们展示了 UHRF1 调节雄性减数分裂。 UHRF1缺陷导致减数分裂失败和男性不育。从机制上讲，UHRF1 的缺乏显着改变了精母细胞的减数分裂基因谱。 Uhrf1 敲除导致整体 5hmC 水平升高。 hyper-5hmC 在转录起始位点 (TSS) 的富集与基因下调高度相关。此外，TET1酶水平升高可能导致Uhrf1敲除精母细胞中5hmC水平升高。最后，我们报道了雄性减数分裂中的关键基因Uhrf1通过下调TET1来抑制hyper-5hmC。此外，UHRF1 促进 RNA 聚合酶 II (RNA-pol2) 加载，从而促进基因转录。因此，我们的研究证明了 5hmC 动态变化的潜在调控机制及其参与雄性减数分裂的表观遗传调控。
5’-hydroxymethylcytosine (5hmC), an important 5’-cytosine modification, is altered highly in order in male meiotic prophase. However, the regulatory mechanism of this dynamic change and the function of 5hmC in meiosis remain largely unknown. Using a knockout mouse model, we showed UHRF1 regulated male meiosis. UHRF1 deficiency led to the failure of meiosis and male infertility. Mechanistically, the deficiency of UHRF1 altered significantly the meiotic gene profile of spermatocytes. Uhrf1 knockout induced an increase of the global 5hmC level. The enrichment of hyper-5hmC at transcriptional start sites (TSSs) was highly associated with gene down-regulation. In addition, the level of the TET1 enzyme elevated might have contributed to the higher 5hmC level in the Uhrf1 knockout spermatocytes. Finally, we reported Uhrf1, a key gene in male meiosis, repressed hyper-5hmC by down-regulating TET1. Furthermore, UHRF1 facilitated RNA polymerase II (RNA-pol2) loading to promote gene transcription. Thus, our study demonstrated a potential regulatory mechanism of the 5hmC dynamic change and its involvement in epigenetic regulation in the male meiosis.