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

Nat Commun. 2013:4:1754. doi: 10.1038/ncomms2780.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 Methyltransferases
  • 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
  • RNA Interference
  • Repressor Proteins
  • Spermatogenesis / genetics
  • Time Factors
  • Up-Regulation / genetics

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Biomarkers
  • Histones
  • Repressor Proteins
  • Max protein, mouse
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Ddx4 protein, mouse
  • DEAD-box RNA Helicases
  • Lysine

Associated data

  • GEO/GSE45181