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

• Published in: Nature communications Vol. 12; no. 1; p. 3184
• Main Authors: Horisawa-Takada, Yuki, Kodera, Chisato, Takemoto, Kazumasa, Sakashita, Akihiko, Horisawa, Kenichi, Maeda, Ryo, Shimada, Ryuki, Usuki, Shingo, Fujimura, Sayoko, Tani, Naoki, Matsuura, Kumi, Akiyama, Tomohiko, Suzuki, Atsushi, Niwa, Hitoshi, Tachibana, Makoto, Ohba, Takashi, Katabuchi, Hidetaka, Namekawa, Satoshi H., Araki, Kimi, Ishiguro, Kei-Ichiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/51; 14; 14/32; 38; 38/15; 38/22; 38/23; 38/39; 38/88; 631/136/2434/1822; 631/80/641/1633; 64/60; 82/1; 82/58; Animals; Biological activity; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromatin; Chromatin Immunoprecipitation Sequencing; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Disease Models, Animal; Female; Gametocytes; Gene expression; Gene regulation; Histone Deacetylase 1 - metabolism; Histone Deacetylase 2 - metabolism; Humanities and Social Sciences; Humans; Infertility, Male - genetics; Male; Meiosis; Mice; Mice, Knockout; multidisciplinary; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oocytes - cytology; Oocytes - metabolism; Pachytene; Pachytene Stage - genetics; Potassium Channels, Voltage-Gated - genetics; Potassium Channels, Voltage-Gated - metabolism; Prophase; Proteins; RNA-Seq; Science; Science (multidisciplinary); Spermatids - cytology; Spermatids - metabolism; Spermatocytes; Spermatogenesis; Spermatogenesis - genetics; Transcription; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transcriptomes; Zebrafish; Zinc finger proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-23378-4

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. The authors add to our knowledge of the transcriptional regulation of the meiotic program in mice spermatocytes, showing ZFP541 regulates meiotic prophase and transition to the division phase by being the target for upstream factors MEIOSIN/STRA8.