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. Copyright © 2003 John Wiley & Sons, Ltd.