Saccharomyces cerevisiae Set1p is a methyltransferase specific for lysine 4 of histone H3 and is required for efficient gene expression

Yeast. 2003 Jul 15;20(9):827-35. doi: 10.1002/yea.995.


Several homologues of the Drosophila Su(var)3-9 protein were recently reported to methylate lysine 9 of histone H3. Whereas this methylation signal served to recruit heterochromatin-associated proteins to transcriptionally silenced regions, histone H3 methylated at lysine 4 was associated with transcriptionally active areas of the genome. These findings suggested that the interplay between lysine 4 and 9 methylation is crucial in eukaryotic gene regulation. Here we provide evidence that Saccharomyces cerevisiae Set1p is a methyltransferase specific for lysine 4 of histone H3. In addition, we show that the absence of Set1p and lysine 4 methylation result in decreased transcription of approximately 80% of the genes in S. cerevisiae. Hierarchical clustering analysis of the set1(-) expression profile revealed a correspondence to that of a mad2(-) strain, suggesting that the transcriptional defect in the set1(-) strain may be due to changes in chromatin structure. These findings establish a central role for methylation of histone H3 lysine 4 in transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cluster Analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Enzymologic / physiology*
  • Gene Expression Regulation, Fungal / physiology*
  • Histone-Lysine N-Methyltransferase
  • Histones / metabolism*
  • Lysine / metabolism*
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • RNA, Fungal / chemistry
  • RNA, Fungal / genetics
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / physiology


  • DNA-Binding Proteins
  • Histones
  • RNA, Fungal
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • SET1 protein, S cerevisiae
  • Lysine