Stra8在精子发生过程中至关重要，Stra8基因敲除小鼠表现为雄性不育，但Stra8的分子作用机制至今尚未阐明。应用酵母双杂交技术，我们筛选出一个与Stra8相互作用的蛋白-Setd8。Setd8是目前发现的唯一一种H4K20单甲基化酶，其缺失可致细胞周期阻滞等严重发育障碍，因而在细胞中发挥极为重要的作用。为此，本项目拟开展以下四方面的研究：1）Stra8与Setd8相互作用机制分析。明确两者之间的转录调控关系，确定两者相互作用的关键区域；2）研究体外培养生精细胞中Stra8在细胞周期、DNA损伤修复及转录调控三方面的作用机制；3）在体研究减数分裂前生精细胞中Stra8在细胞周期、DNA损伤修复及转录调控三方面的的作用机制；4）研究Stra8与男性不育症之间的相关性。通过上述系列研究，揭示Stra8和Setd8调控精子发生的分子机制，为男性不育症临床诊断和治疗提供理论基础和实践的可能性。

Stra8 is essential for spermatogenesis. Stra8-knockout males are infertile. But the molecular machanism of Stra8 during spermatogenesis remains elusive.Using yeast two-hybrid system, we identified Setd8 as a novel interacting partner of Stra8. Setd8 is the sole histone methytransferase responsible for the monomethylation of histone H4 lysine 20(H4K20me1).The depletion of Setd8 resulted in profound cell cycle defects.It is vital to cell viability. In this proposal, studies will be carried out from the following four aspects: 1) Analysis the interaction between Stra8 and Setd8. 2)Analysis the roles of Stra8 in proper cell cycle progression, the DNA damage response and gene transcription in vitro. 3)Analysis the functions of Stra8 in cell cycle, DNA damage response and transcription regulation during meiosis in vivo. 4)Analysis the correlation of Stra8 with male infertile. The above series of studies will reveal the molecular funtions of Stra8 during spermatogenesis by interacting with Setd8. These studies will provide a theoretical basis and practical possibility for the diagnosis and treatment of male infertility.