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

• Published in: Nature communications Vol. 7; no. 1; p. 11056
• Main Authors: Suzuki, Ayumu, Hirasaki, Masataka, Hishida, Tomoaki, Wu, Jun, Okamura, Daiji, Ueda, Atsushi, Nishimoto, Masazumi, Nakachi, Yutaka, Mizuno, Yosuke, Okazaki, Yasushi, Matsui, Yasuhisa, Belmonte, Juan Carlos Izpisua, Okuda, Akihiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-03-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 631/136/532/2117; 631/208/199; 631/80/641/1633; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Ascorbic Acid - pharmacology; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Gametogenesis - drug effects; Gametogenesis - genetics; Gene Expression Regulation, Developmental - drug effects; Gene Knockdown Techniques; Germ Cells - drug effects; Germ Cells - metabolism; Humanities and Social Sciences; Meiosis - drug effects; Meiosis - genetics; Mice; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - drug effects; Mouse Embryonic Stem Cells - metabolism; multidisciplinary; Polycomb-Group Proteins - metabolism; Retinoids - pharmacology; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11056

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.
The mechanisms that trigger meiosis in germ cells and halt this process in non-germline cells are unclear. Here, the authors show that knockout of
Max
in embryonic stem cells results in meiotic onset in a mechanism that involves the PRC1 complex.