Abstract
Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Profiling
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Gene Expression Regulation, Fungal* / drug effects
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Genes, Fungal / genetics*
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Histone-Lysine N-Methyltransferase
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Histones / chemistry
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Histones / immunology
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Histones / metabolism*
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Inositol / pharmacology
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Lysine / metabolism*
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Methionine / pharmacology
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Methylation / drug effects
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects
Substances
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Antibodies
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DNA-Binding Proteins
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Histones
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Inositol
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Methionine
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Histone-Lysine N-Methyltransferase
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SET1 protein, S cerevisiae
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Lysine