Horisawa-Takada et al., Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during 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 novel protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulator for meiotic prophase progression. Our genetic study showed 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 revealed 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 males, 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动态变化。然而，目前仍未明确减数分裂转录程序究竟如何建立，以确保减数分裂前期顺利完成。本研究鉴定出一种新型蛋白质复合物，其由生殖细胞特异性锌指蛋白ZFP541及其互作蛋白KCTD19组成，是调控减数分裂前期进程的关键转录调控因子。本研究的遗传学实验表明，ZFP541与KCTD19自粗线期（pachytene）起共表达，并在睾丸内减数分裂前期程序的完成过程中发挥不可或缺的作用。此外，我们的染色质免疫共沉淀测序（ChIP-seq）与转录组分析结果显示，ZFP541可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塑，进而推动减数分裂后发育进程。