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

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, Kimi Araki and Kei-Ichiro Ishiguro ()
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Yuki Horisawa-Takada: Kumamoto University
Chisato Kodera: Kumamoto University
Kazumasa Takemoto: Kumamoto University
Akihiko Sakashita: Keio University School of Medicine
Kenichi Horisawa: Kyushu University
Ryo Maeda: Osaka University
Ryuki Shimada: Kumamoto University
Shingo Usuki: Kumamoto University
Sayoko Fujimura: Kumamoto University
Naoki Tani: Kumamoto University
Kumi Matsuura: Kumamoto University
Tomohiko Akiyama: Keio University School of Medicine
Atsushi Suzuki: Kyushu University
Hitoshi Niwa: Kumamoto University
Makoto Tachibana: Osaka University
Takashi Ohba: Kumamoto University
Hidetaka Katabuchi: Kumamoto University
Satoshi H. Namekawa: University of California
Kimi Araki: Kumamoto University
Kei-Ichiro Ishiguro: Kumamoto University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23378-4

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