Active genes are tri-methylated at K4 of histone H3.
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.
D000906:Antibodies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D007294:Inositol / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism*; D008715:Methionine / Q000494:pharmacology; D008745:Methylation / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D000906:Antibodies; D004268:DNA-Binding Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D007294:Inositol; D008715:Methionine; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D008239:Lysine