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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0205969
JournalPloS one
Volume13
Issue number11
DOIs
Publication statusPublished - 2018 Nov

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Tatsumi, D., Hayashi, Y., Endo, M., Kobayashi, H., Yoshioka, T., Kiso, K., Kanno, S., Nakai, Y., Maeda, I., Mochizuki, K., Tachibana, M., Koseki, H., Okuda, A., Yasui, A., Kono, T., & Matsui, Y. (2018). DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell- related genes in mouse embryonic stem cells. PloS one, 13(11), [e0205969]. https://doi.org/10.1371/journal.pone.0205969