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Briggs, SD, Bryk, M, Strahl, BD, Cheung, WL, Davie, JK, Dent, SY, Winston, F and Allis, CD (2001) Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. Genes Dev. 15:3286-95


Histone methylation is known to be associated with both transcriptionally active and repressive chromatin states. Recent studies have identified SET domain-containing proteins such as SUV39H1 and Clr4 as mediators of H3 lysine 9 (Lys9) methylation and heterochromatin formation. Interestingly, H3 Lys9 methylation is not observed from bulk histones isolated from asynchronous populations of Saccharomyces cerevisiae or Tetrahymena thermophila. In contrast, H3 lysine 4 (Lys4) methylation is a predominant modification in these smaller eukaryotes. To identify the responsible methyltransferase(s) and to gain insight into the function of H3 Lys4 methylation, we have developed a histone H3 Lys4 methyl-specific antiserum. With this antiserum, we show that deletion of SET1, but not of other putative SET domain-containing genes, in S. cerevisiae, results in the complete abolishment of H3 Lys4 methylation in vivo. Furthermore, loss of H3 Lys4 methylation in a set1 Delta strain can be rescued by SET1. Analysis of histone H3 mutations at Lys4 revealed a slow-growth defect similar to a set1 Delta strain. Chromatin immunoprecipitation assays show that H3 Lys4 methylation is present at the rDNA locus and that Set1-mediated H3 Lys4 methylation is required for repression of RNA polymerase II transcription within rDNA. Taken together, these data suggest that Set1-mediated H3 Lys4 methylation is required for normal cell growth and transcriptional silencing.


PubMed PMC312847 Online version:10.1101/gad.940201


Animals; Antibody Formation; Blotting, Western; Cell Division; DNA Primers/chemistry; DNA, Bacterial/genetics; DNA, Ribosomal/genetics; DNA-Binding Proteins/metabolism; Fungal Proteins/metabolism; Gene Silencing; Genetic Vectors; Heterochromatin/chemistry; Heterochromatin/metabolism; Histone-Lysine N-Methyltransferase; Histones/metabolism; Lysine/metabolism; Methylation; Methyltransferases/genetics; Methyltransferases/metabolism; Mutation; Nucleosomes/chemistry; Nucleosomes/metabolism; Polymerase Chain Reaction; Precipitin Tests; Protein Methyltransferases; RNA Polymerase III/metabolism; Rabbits; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins; Transcription Factors/metabolism



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0051568: histone H3-K4 methylation



Figure3A and C

CACAO 11080


GO:0042800: histone methyltransferase activity (H3-K4 specific)



Figure 3A and C

CACAO 11081


See also


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