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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / embryology*
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Caenorhabditis elegans / enzymology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans Proteins / analysis
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Embryo, Nonmammalian / enzymology
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Embryonic Development / genetics
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Female
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Gene Expression Regulation, Developmental*
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Gene Silencing
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Germ Cells / cytology
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Germ Cells / metabolism*
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase / analysis
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Histone-Lysine N-Methyltransferase / genetics
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Histone-Lysine N-Methyltransferase / metabolism*
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Histones / metabolism
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Male
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Meiosis / genetics
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Methylation
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Mitosis / genetics
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Nuclear Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Polycomb-Group Proteins
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Protein Methyltransferases
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Transcription, Genetic
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X Chromosome / genetics*
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X Chromosome / metabolism
Substances
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Caenorhabditis elegans Proteins
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Histones
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Mes-3 protein, C elegans
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Mes-4 protein, C elegans
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Nuclear Proteins
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Polycomb-Group Proteins
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mes-2 protein, C elegans
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mes-6 protein, C elegans
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Histone Methyltransferases
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Protein Methyltransferases
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Histone-Lysine N-Methyltransferase