Max is a repressor of germ cell-related gene expression in mouse embryonic stem cells

Ikuma Maeda, Daiji Okamura, Yuko Tokitake, Makiko Ikeda, Hiroko Kawaguchi, Nathan Mise, Kuniya Abe, Toshiaki Noce, Akihiko Okuda and Yasuhisa Matsui ()
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Ikuma Maeda: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University
Daiji Okamura: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University
Yuko Tokitake: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University
Makiko Ikeda: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University
Hiroko Kawaguchi: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University
Nathan Mise: Mammalian Cellular Dynamics, RIKEN BioResource Center
Kuniya Abe: Mammalian Cellular Dynamics, RIKEN BioResource Center
Toshiaki Noce: School of Medicine, Keio University
Akihiko Okuda: Research Center for Genomic Medicine, Saitama Medical University
Yasuhisa Matsui: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Embryonic stem cells and primordial germ cells (PGCs) express many pluripotency-associated genes, but embryonic stem cells do not normally undergo conversion into primordial germ cells. Thus, we predicted that there is a mechanism that represses primordial germ cell-related gene expression in embryonic stem cells. Here we identify genes involved in this putative mechanism, by using an embryonic stem cell line with a Vasa reporter in an RNA interference screen of transcription factor genes expressed in embryonic stem cells. We identify five genes that result in the expression of Vasa when silenced. Of these, Max is the most striking. Transcriptome analysis reveals that Max knockdown in embryonic stem cells results in selective, global derepression of germ cell-specific genes. Max interacts with histone H3K9 methyltransferases and associates with the germ cell-specific genes in embryonic stem cells. In addition, Max knockdown results in a decrease in histone H3K9 dimethylation at their promoter regions. We propose that Max is part of protein complex that acts as a repressor of germ cell-related genes in embryonic stem cells.

Date: 2013
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DOI: 10.1038/ncomms2780

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