UC San Diego

Covalent modifications of chromatin regulate genomic structure and accessibility in diverse biological processes such as transcriptional regulation, cell cycle progression, and the DNA damage response. Whereas many histone modifications have been characterized, understanding the interactions between these and their combinatorial effects remains an active area of investigation, including dissecting functional interactions between enzymes mediating these modifications. In budding yeast, the histone acetyltransferase Gcn5 interacts with Rts1, the regulatory subunit of protein phosphatase 2A (PP2A), in part via the dynamic phosphorylation of conserved residues on histone H2B and the centromeric-specific histone H3 variant, Cse4. To further probe these dynamics, we sought to identify kinases which might contribute and found a role for a stress-activated protein kinase, Hog1. Deletion of HOG1 (hog1∆) rescues gcn5∆ sensitivity to the microtubule poison nocodazole and the lethality of the gcn5∆ rts1∆ double mutant. Dynamic phosphorylation of histone H2B-T91 also functions in the Hog1-Gcn5 interaction. Furthermore, Loss of HOG1 decreases aneuploidy and apoptotic populations in gcn5∆ cells. Together, these results suggest that Hog1 functionally opposes Gcn5 and Rts1 in the context of the spindle assembly checkpoint and raise the possibility of further kinase involvement in GCN5’s functions.