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

Nat Commun. 2016 Mar 30;7:11056. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Meiosis / drug effects
  • Meiosis / genetics*
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / drug effects
  • Mouse Embryonic Stem Cells / metabolism*
  • Polycomb-Group Proteins / metabolism
  • Retinoids / pharmacology


  • Adaptor Proteins, Signal Transducing
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Polycomb-Group Proteins
  • Retinoids
  • Stra8 protein, mouse
  • Max protein, mouse
  • Ascorbic Acid