Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis

减数分裂特异性 ZFP541 阻遏物复合物促进小鼠精子发生过程中减数分裂前期的发育进程直至完成

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作者:Yuki Horisawa-Takada, Chisato Kodera #, Kazumasa Takemoto #, Akihiko Sakashita, Kenichi Horisawa, Ryo Maeda, Ryuki Shimada, Shingo Usuki, Sayoko Fujimura, Naoki Tani, Kumi Matsuura, Tomohiko Akiyama, Atsushi Suzuki, Hitoshi Niwa, Makoto Tachibana, Takashi Ohba, Hidetaka Katabuchi, Satoshi H Namekawa

Abstract

During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify 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 a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development.

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