The Saccharomyces cerevisiae protein Set1 is a histone methylase which specifically targets lysine 4 on the N-terminal tail of histone H3. It can catalyse the addition of both a di-methyl or a tri-methyl group. There has been some evidence suggesting a role for Set1 in transcriptional regulation and in silencing but its biological function remains unclear.

In Ng and Robert et al., we used ChIP as well as DNA microarray technologies to investigate the function of Set1 in wild type yeast cells. We found that Set1 associates with transcriptionally active Pol II genes in yeast cells. Set1 association is directly related to the level of transcriptional activity, and it can be rapidly regulated. Unexpectedly, Set1 does not associate with promoters, but rather is targeted to the 5' portion of mRNA coding regions, a novel localization pattern suggesting that Set1 is recruited by the Pol II elongation machinery. Set1 association is dependent on Kin28, a serine kinase that phosphorylates Pol II and Set1 interacts with Pol II in vivo. Although the level di-methylated H3-K4 is relatively uniform throughout the genome, the pattern of tri-methylated H3-K4 strongly correlates with Set1 occupancy. Interestingly, di-methylated and, to a lesser extent, tri-methylated H3-K4 at the proximal coding region persists for considerable time after Set1 dissociates from the chromatin, suggesting that H3-K4 methylation can provide a molecular memory of transcriptional activity.