The multiple faces of Set1

In Saccharomyces cerevisiae, H3 methylation at lysine 4 (H3K4) is mediated by Set1. Set1 is a large protein bearing a conserved RNA recognition motif in addition to its catalytic C-terminal SET domain. The SET and RRM domains are conserved in Set1 orthologs from yeast to humans. Set1 belongs to a complex of 8 proteins, also showing a striking conservation, most subunits being required to efficiently catalyze methylation of H3K4. The deletion of SET1 is not lethal but has pleiotropic phenotypes. It affects growth, transcriptional activation, repression and elongation, telomere length regulation, telomeric position effect, rDNA silencing, meiotic differentiation, DNA repair, chromosome segregation, and cell wall organization. In this review, we discuss the regulation of H3K4 methylation and try to link Set1 activity with the multiple phenotypes displayed by cells lacking Set1. We also suggest that Set1 may have multiple targets.