最近两年基于ATAC-seq等新技术的研究相继报道了精子发生过程中发生了动态的染色质重塑过程，从而揭示了新的、生殖细胞特异转录组的调控机理。该染色质重塑调控机理仍不清楚。我们发现染色质重塑因子Znhit1在睾丸中高表达，小鼠生殖细胞中Znhit1敲除导致精母细胞DSB修复异常与无精症的产生。此外在粗线期，组蛋白变体H2A.Z与联会复合体蛋白SYCP3存在共定位，而Znhit1缺失导致联会复合体上H2A.Z信号的消失。我们还发现生精细胞H2A.Z的敲除也导致小鼠无精症的产生。因此我们提出以下假说：Znhit1通过H2A.Z参与减数分裂阶段的染色质重塑，并因此在DSB产生与修复中发挥作用。我们计划研究该假说，并发现这两个基因调节减数分裂的功能及其机理；还将对生育人群、无精症与少精症患者Znhit1基因的全外显子进行测序，研究Znhit1突变与此不育症的关系，为其临床诊断与治疗提供新的候选基因。

It has been reported very recently that male germ cells undergo dynamic chromatin remodeling, by using ATAC-seq, highlighting a novel regulatory mechanism for highly diverse transcriptomes, which are required for the production of functional sperm. However, it remains unknown how germline chromatin is organized to promote the dynamic, complex transcriptomes of spermatogenesis. We found that Znhit1, an important subunit of chromatin remodeler SRCAP complex, is highly expressed in testis, and the mice with germ-cell-specific knockout of Znhit1. have the small sizes of testis (about 35-40% of control) and the epididymis where no detectable sperm exist. Deficiency of Znhit1 cause an impaired DSB repairing in the prophase of Meiosis I. Importantly, histone H2A.Z, a variant of H2A, is observed to be co-localized with SYCP3, the marker of synapsis complex in Pachytene, but vast majority of signal of H2A.Z disappears in the presence of Znhit1 deficiency. Interestingly, we also found the male mice with homozygous deletion of H2A.Z are infertile, with no detectable sperm in epididymis. Therefore, we propose the following hypothesis: by loading H2A.Z on nucleosomes, Znhit1 plays a key role in dynamic chromatin remodeling in meiosis which is required for DSB repairing. We plan to take a systematic study via using diverse methods including ATAC-seq and CHIP-seq, in order to approach the hypothesis. Finally, we will also study genetic association of single nucleotide polymorphism of Znhit1 and clinical azoospermia and oligozoospermia, in order to understand whether genetic variations of Znhit1 contribute development of male infertility.