Open AccessDNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell–related genes in mouse embryonic stem cells
Author(s) -
Daiki Tatsumi,
Yohei Hayashi,
Mai Endo,
Hisato Kobayashi,
Takumi Yoshioka,
Kohei Kiso,
Shin-ichiro Kanno,
Yuji Nakai,
Ikuma Maeda,
Kentaro Mochizuki,
Makoto Tachibana,
Haruhiko Koseki,
Akihiko Okuda,
Akira Yasui,
Toru Kono,
Yasuhisa Matsui
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205969
Subject(s) - biology , methyltransferase , dna methylation , epigenetics , histone methyltransferase , histone methylation , germ cell , regulation of gene expression , polycomb group proteins , histone , embryonic stem cell , gene , genetics , gene expression , repressor , microbiology and biotechnology , methylation
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.