@article{63670c0f0f1d46fdbab7581caace7a34,
title = "MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells",
abstract = "The mechanisms regulating meiotic initiation in mammals are enigmatic. It is known that retinoic acid (RA) signaling plays a pivotal role during meiotic initiation. STRA8, which is expressed in response to RA, is thought to be a key factor promoting meiotic initiation. However, the specific role of STRA8 in meiotic initiation has remained elusive. Here, we identified MEIOSIN as a germ-cell-specific factor that associates with STRA8. MEIOSIN, like STRA8, is expressed in response to RA and plays an essential role in meiotic initiation in both males and females. Functional analyses revealed that MEIOSIN acts as a transcription factor together with STRA8, and that both factors are critical for driving meiotic gene activation. Furthermore, temporally restricted expression of MEIOSIN leads to meiotic entry decision during spermatogenesis. The present study demonstrates that MEIOSIN, in collaboration with STRA8, plays a central role in regulating the mitosis to meiosis germ cell fate decision in mammals. Although meiosis is a fundamental and well-studied biological process, the molecular mechanisms regulating its initiation are poorly understood. Ishiguro et al. identify MEIOSIN as a key initiator of meiosis and elucidate a framework for understanding how switching of the cell cycle from mitosis to meiosis occurs in the mammalian germline.",
keywords = "STRA8, cell cycle, germ cell, meiosis, meiotic recombination, retinoic acid, retinoic acid chromosome, spermatogenesis, synaptonemal complex",
author = "Ishiguro, {Kei ichiro} and Kumi Matsuura and Naoki Tani and Naoki Takeda and Shingo Usuki and Mariko Yamane and Michihiko Sugimoto and Sayoko Fujimura and Mihoko Hosokawa and Shinichiro Chuma and Ko, {Minoru S.H.} and Kimi Araki and Hitoshi Niwa",
note = "Funding Information: The authors thank Takashi Seki (Liaison Laboratory Research Promotion Center, IMEG, Kumamoto University), Etsushi Kitamura, and Hiromi Kimura for technical support, and Minetaro Ogawa, Masatake Araki, and Narumi Koga for provision of materials. GS (DBA/2) and ES (KY1.1) cell lines were kindly provided by Drs. Takashi Shinohara and Junji Takeda, respectively. The authors also thank Drs. Marry Ann Handel, David Page, Shosei Yoshida, Kodai Hirano, Yumiko Saga, Akira Nakamura, Tsutomu Endo, Yoshinori Watanabe, and Satoshi Namekawa for their valuable discussion. This work was supported in part by KAKENHI grant #19H05748 (to H.N.), KAKENHI grant #16H01257, #16H01221, #17H03634, #18K19304, #19H05245, #19H05743, and #JP 16H06276 from MEXT, Japan; NIG-JOINT (44A2017, 40A2018, and 32A2019); the program of the Joint Usage/ IMEG Research Center for Developmental Medicine; Takeda Science Foundation; Yamada Science Foundation; Ichiro Kanehara Foundation for Medical Science and Medical Care (to K.I.). K.I. conducted the study, performed most of the experiments in mice, and wrote the manuscript. N. Takeda, M.S. and K.A. generated Stra8-3FH-GFP KI mouse, Meiosin KO, and Stra8 KO mice. N. Tani performed the mass spectrometry analysis. K.M. and H.N. performed the MEIOSIN and STRA8 ChIP-seq analysis in mouse testes. S.U. and M.Y. performed the RNA-seq and SMART-seq analysis. M.H. and S.C. performed the ChIP-seq and RNA-seq in GS cells. H.N. conducted the homolog search. M.S.H.K. supported the study. M.S. and K.I. performed embryonic gonad experiments. N. Takeda and K.I. performed GV oocyte experiments. S.F. performed histological analysis. The experimental design and interpretation of data were conducted by K.I. K.A. and H.N. The authors declare no competing interests. Funding Information: The authors thank Takashi Seki (Liaison Laboratory Research Promotion Center, IMEG, Kumamoto University), Etsushi Kitamura, and Hiromi Kimura for technical support, and Minetaro Ogawa, Masatake Araki, and Narumi Koga for provision of materials. GS (DBA/2) and ES (KY1.1) cell lines were kindly provided by Drs. Takashi Shinohara and Junji Takeda, respectively. The authors also thank Drs. Marry Ann Handel, David Page, Shosei Yoshida, Kodai Hirano, Yumiko Saga, Akira Nakamura, Tsutomu Endo, Yoshinori Watanabe, and Satoshi Namekawa for their valuable discussion. This work was supported in part by KAKENHI grant # 19H05748 (to H.N.), KAKENHI grant # 16H01257 , # 16H01221 , # 17H03634 , # 18K19304 , # 19H05245 , # 19H05743 , and #JP 16H06276 from MEXT , Japan; NIG -JOINT ( 44A2017 , 40A2018 , and 32A2019 ); the program of the Joint Usage/ IMEG Research Center for Developmental Medicine ; Takeda Science Foundation ; Yamada Science Foundation ; Ichiro Kanehara Foundation for Medical Science and Medical Care (to K.I.). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = feb,
day = "24",
doi = "10.1016/j.devcel.2020.01.010",
language = "English",
volume = "52",
pages = "429--445.e10",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "4",
}