Saccharomyces cerevisiae Set1p is a methyltransferase specific for lysine 4 of histone H3 and is required for efficient gene expression.
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.
Boa
Simon
S
Room 427A, Molecular Biology Building, Department of Molecular and Cellular Biology, University of Cape Town, University Private Bag, Rondebosch 7700, South Africa.
Coert
Claudette
C
Patterton
Hugh-G
HG
D000595:Amino Acid Sequence; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
D004268:DNA-Binding Proteins; D006657:Histones; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D008239:Lysine