Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells

Ayumu Suzuki, Masataka Hirasaki, Tomoaki Hishida, Jun Wu, Daiji Okamura, Atsushi Ueda, Masazumi Nishimoto, Yutaka Nakachi, Yosuke Mizuno, Yasushi Okazaki, Yasuhisa Matsui, Juan Carlos Izpisua Belmonte*, Akihiko Okuda

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division. Furthermore, our analyses uncovers that Max expression is transiently attenuated in germ cells undergoing meiosis in vivo and its forced reduction induces meiosis-like cytological changes in cultured germline stem cells. Mechanistically, Max depletion alterations are, in part, due to impairment of the function of an atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data highlight MAX as a new regulator of meiotic onset.

Original languageEnglish (US)
Article number11056
JournalNature Communications
Volume7
DOIs
StatePublished - Mar 30 2016

Bibliographical note

Funding Information:
Acknowledgements We thank Dr Minoru S.H. Ko and Tomoko Okuda for the reporter plasmid bearing the Zscan4 gene promoter and technical assistance, respectively. We are also indebted to Drs Takashi Shinohara, Mitinori Saitou, Hiroyuki Sasaki and Hiroaki Ohishi for their helpful discussions. This study was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and primarily by a Grant-in-Aid for the Support Project of Strategic Research at Private Universities to the Saitama Medical University, Research Center for Genomic Medicine. A.O. is the recipient of grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI (grants numbers 25293082, 25670147 and 26112512). A.S. is supported by a grant from JSPS KAKENHI (grant number 26670162). Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, Universidad Católica San Antonio de Murcia (UCAM), and The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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