Set2-catalyzed methylation of histone H3 represses basal expression of GAL4 in Saccharomyces cerevisiae.

Recent work has shown that histone methylation is an important regulator of transcription. While much is known about the roles of histone methyltransferases (HMTs) in the establishment of heterochromatin, little is known of their roles in the regulation of actively transcribed genes. We describe an in vivo role of the Saccharomyces cerevisiae HMT, Set2. We identified SET2 as a gene necessary for repression of GAL4 basal expression and show that the evolutionarily conserved SACI, SACII, and SET domains of Set2 are necessary for this repression. We confirm that Set2 catalyzes methylation of lysine 36 on the N-terminal tail of histone H3. Conversion of lysine 36 to an unmethylatable arginine causes a decrease in the repression of GAL4 transcription, as does a Delta set2 mutation. We further show that lysine 36 of histone H3 at GAL4 is methylated and that this methylation is dependent upon the presence of SET2.