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

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 embryo...

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Bibliographic Details
Published in:Nature communications 2013, Vol.4 (1), p.1754-1754, Article 1754
Main Authors: Maeda, Ikuma, Okamura, Daiji, Tokitake, Yuko, Ikeda, Makiko, Kawaguchi, Hiroko, Mise, Nathan, Abe, Kuniya, Noce, Toshiaki, Okuda, Akihiko, Matsui, Yasuhisa
Format: Article
Language:English
Subjects:
Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism
Biomarkers - metabolism
Cell Line
DEAD-box RNA Helicases - genetics
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Flow Cytometry
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Genes, Reporter
Germ Cells - cytology
Germ Cells - metabolism
Histone-Lysine N-Methyltransferase - metabolism
Histones - metabolism
Lysine - metabolism
Meiosis - genetics
Methylation
Mice
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic - genetics
Protein Binding
Repressor Proteins
RNA Interference
Spermatogenesis - genetics
Time Factors
Up-Regulation - genetics
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Summary: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.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms2780