title: Max is a repressor of germ cell-related gene expression in mouse embryonic stem cells.
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.
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Ikuma
authors.initials: I
authors.lastname: Maeda
authors.forename: Daiji
authors.initials: D
authors.lastname: Okamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tokitake
authors.forename: Makiko
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Nathan
authors.initials: N
authors.lastname: Mise
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Noce
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuda
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Matsui
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008540:Meiosis / Q000235:genetics; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012097:Repressor Proteins; D013091:Spermatogenesis / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015415:Biomarkers; D006657:Histones; D012097:Repressor Proteins; C068422:Max protein, mouse; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C090864:Ddx4 protein, mouse; D053487:DEAD-box RNA Helicases; D008239:Lysine