MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line

Development. 2006 Oct;133(19):3907-17. doi: 10.1242/dev.02584.

Abstract

Germ cell development in C. elegans requires that the X chromosomes be globally silenced during mitosis and early meiosis. We previously found that the nuclear proteins MES-2, MES-3, MES-4 and MES-6 regulate the different chromatin states of autosomes versus X chromosomes and are required for germline viability. Strikingly, the SET-domain protein MES-4 is concentrated on autosomes and excluded from the X chromosomes. Here, we show that MES-4 has histone H3 methyltransferase (HMT) activity in vitro, and is required for histone H3K36 dimethylation in mitotic and early meiotic germline nuclei and early embryos. MES-4 appears unlinked to transcription elongation, thus distinguishing it from other known H3K36 HMTs. Based on microarray analysis, loss of MES-4 leads to derepression of X-linked genes in the germ line. We discuss how an autosomally associated HMT may participate in silencing genes on the X chromosome, in coordination with the direct silencing effects of the other MES proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / analysis
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Embryo, Nonmammalian / enzymology
  • Embryonic Development / genetics
  • Female
  • Gene Expression Regulation, Developmental*
  • Gene Silencing
  • Germ Cells / cytology
  • Germ Cells / metabolism*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / analysis
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism
  • Male
  • Meiosis / genetics
  • Methylation
  • Mitosis / genetics
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Polycomb-Group Proteins
  • Protein Methyltransferases
  • Transcription, Genetic
  • X Chromosome / genetics*
  • X Chromosome / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Histones
  • Mes-3 protein, C elegans
  • Mes-4 protein, C elegans
  • Nuclear Proteins
  • Polycomb-Group Proteins
  • mes-2 protein, C elegans
  • mes-6 protein, C elegans
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase