Horisawa-Takada et al., Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis

During spermatogenesis, meiosis is accompanied by robust alteration in gene expression and chromatin status. However, it remained elusive how meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identified a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulator for mouse meiotic prophase progression. Our genetic studies show that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses reveal that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that germ-cell specific complex that contains ZFP541-KCTD19 promotes the progression of meiotic prophase towards completion in male, and triggers the reconstruction of the transcription network and chromatin organization leading to post-meiotic development.在精子发生过程中，减数分裂伴随基因表达与染色质状态的剧烈改变。然而，目前尚不清楚如何构建减数分裂转录程序以保障减数分裂前期顺利完成。本研究鉴定出一种由生殖细胞特异性锌指蛋白ZFP541（germ-cell-specific zinc-finger protein ZFP541）及其互作蛋白KCTD19组成的蛋白质复合物，其作为调控小鼠减数分裂前期进程的关键转录因子。遗传学研究表明，ZFP541与KCTD19自粗线期起共表达，并在睾丸内减数分裂前期程序的完成中发挥不可或缺的作用。此外，染色质免疫共沉淀测序（ChIP-seq）与转录组分析显示，ZFP541结合并抑制一系列功能与转录调控及共价染色质修饰生物学过程相关的广泛基因。本研究证实，包含ZFP541-KCTD19的生殖细胞特异性复合物可促进雄性个体减数分裂前期向完成阶段推进，并触发转录网络与染色质组织的重构，进而推动减数分裂后发育进程。