组蛋白去乙酰化酶HDAC3在精子发生中的功能和相关机制

表观遗传修饰（Epigenetic modifications）在胚胎发育、干细胞分化和配子发生过程中发挥了重要的调控作用。出生后雄性配子发生包括精原干细胞自我更新，精母细胞的减数分裂和精子细胞的变形成熟，同时伴随着DNA甲基化、组蛋白甲基化和组蛋白乙酰化等的动态变化。HDAC3是一个调控组蛋白乙酰化修饰的去乙酰化酶，而它在精子发生中的功能以及如何和其他表观遗传因子特异性组合来调控染色质活性等还没有研究报道。目前，我们通过睾丸条件性敲除Hdac3基因的小鼠模型，以及通过转录组深度测序（RNA-seq），免疫沉淀（IP）和染色质免疫沉淀结合深度测序（ChIP-seq）等方法，捕获HDAC3靶向结合序列和揭示HDAC3在精子发生中的作用机制，结合PolⅡ和H3K9ac的ChIP-seq探讨Hdac3敲除对基因转录组活性和染色质组蛋白乙酰化的影响。项目的开展有助于理解精子发生中的表观遗传机制。

Epigenetic modifications are essential for embryonic development, stem cells differentiation and gametes formation. Spermatogenesis is a complicated process which includes spermatogonial stem cells self-renewal, meiosis and spermiogenesis, during which dramatic changes in DNA methylation and histone modification occur. HDAC3 is an important histone deacetylase which regulates histone acetylation, however, its precise role in spermatogenesis and how it interacts with other epigenetic modifiers to influence chromatin remains to be identified. Here, we generated Hdac3 conditional knockout mice, we sought to determine genome-wide HDAC3 binding sites by ChIP-seq and analyze the potential mechanisms by immunoprecipitation and RNA deep-sequencing. We will further investigate the changes in transcriptome and histone acetylation in Hdac3 conditional knock-out mice by Pol II ChIP-seq and H3K9ac ChIP-seq. Our proposed project will improve understanding of germ cells specific epigenetic mechanism.