title: Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells.
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.
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Hirasaki
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.|Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hishida
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-9863-1668
authors.initials: J
authors.lastname: Wu
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.|Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, No. 135, Guadalupe, 30107 Murcia, Spain.
authors.forename: Daiji
authors.initials: D
authors.lastname: Okamura
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ueda
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Nishimoto
authors.affiliation: Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.|Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakachi
authors.affiliation: Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.|Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.|Japan Agency for Medical Research and Development and Development-Core Research for Evolutionary Science and Technology (AMED-CREST), Tokyo 100-0004, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005718:Gametogenesis / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005854:Germ Cells / Q000187:drug effects / Q000378:metabolism*; D008540:Meiosis / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D063146:Polycomb-Group Proteins; D012176:Retinoids; C102019:Stra8 protein, mouse; C068422:Max protein, mouse; D001205:Ascorbic Acid