PLoS ONE (Jan 2018)

DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells.

  • Daiki Tatsumi,
  • Yohei Hayashi,
  • Mai Endo,
  • Hisato Kobayashi,
  • Takumi Yoshioka,
  • Kohei Kiso,
  • Shinichiro Kanno,
  • Yuji Nakai,
  • Ikuma Maeda,
  • Kentaro Mochizuki,
  • Makoto Tachibana,
  • Haruhiko Koseki,
  • Akihiko Okuda,
  • Akira Yasui,
  • Tomohiro Kono,
  • Yasuhisa Matsui

DOI
https://doi.org/10.1371/journal.pone.0205969
Journal volume & issue
Vol. 13, no. 11
p. e0205969

Abstract

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In embryonic stem cells (ESCs), the expression of development-related genes, including germ cell-related genes, is globally repressed. The transcription factor MAX represses germ cell-related gene expression in ESCs via PCGF6-polycomb repressive complex 1 (PRC1), which consists of several epigenetic factors. However, we predicted that MAX represses germ cell-related gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and the histone methyltransferase SETDB1 cooperatively control germ cell-related gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cell-related genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cell-related genes in ESCs.