Insights into Transcriptional Regulation by Individual H3K4 Methylation Marks in S. Cerevisiae
Institutional Repository Document
Overview
Research
Identity
Other
View All
Overview
abstract
AbstractSet1 is a lysine methyltransferase in S. cerevisiae that catalyzes the mono, di and tri methylation of the fourth lysine on the amino terminal tail of histone H3 (H3K4). Set1-like methyltransferases are evolutionarily conserved, and research has linked their function to developmental gene regulation and several cancers in higher eukaryotes. Set1 is a member of the multiprotein COMPASS complex in S. cerevisiae. The H3K4 methylation activity of COMPASS regulates gene expression and chromosome segregation in vivo. The three distinct methyl marks on histone H3K4 act in discrete ways to regulate transcription. Trimethylation of H3K4 is usually associated with active transcription whereas dimethylation of H3K4 is associated with gene repression. In this study, amino acid substitution mutants of SET1 that encode partial function Set1 proteins capable of H3K4me1, H3K4me1 and H3K4me2, or H3K4me1and H3K4me3 were analyzed to learn more about the roles of individual H3K4 methyl marks in transcription. The findings reveal a previously unappreciated role for H3K4me1 in activation of transcription of the HIS3 gene in S. cerevisiae cultures grown under histidine-starvation conditions. Surprisingly, induction of the HIS3 gene in cultures grown under histidine starvation is not accompanied by significant changes in the profiles of H3K4-methylated nucleosomes at the HIS3 gene in SET1 wild-type strains and set1 partial-function mutants. The data show that H3K4me1 supports induction of HIS3 mRNA to wild-type levels under histidine-starvation conditions and that higher-order H3K4 methylation (H3K4me2 and H3K4me3) is not required.
