SRA

H2A.Z acetylation has been suggested to regulate genes but effects on gene expression globally have not been reported. We find that the H2A.Z acetylation sites are required for normal growth in the presence of caffeine and therefore examined the gene expression response to caffeine when H2A.Z can't be acetylated. Surprisingly we found little or no change in gene induction but a marked failure to remove H2A.Z from activated promoters. Caffeine causes a proteasome-dependent degradation of H2A.Z that is impaired in the absence of the H2A.Z acetylation sites. The proteasomal regulator Blm10 that has previously been implicated in acetylation-dependent histone degradation is required for H2A.Z degradation, revealing a novel role for acetylation in regulating H2A.Z protein levels. When H2A.Z levels are raised, either through loss of the acetylation sites or overexpression of the protein, a shared set of genes aberrantly retains H2A.Z at their 5' ends during the caffeine response. As a result, expression of these genes fails to return to normal levels. H2A.Z is therefore subject to post-translational proteasomal regulation that controls protein levels, and the fine-tuning of gene expression during a stress response requires the normal function of this pathway. This regulation of H2A.Z degradation by acetylation is a previously unrecognised aspect of gene regulation. Overall design: H2A.Z occupancy and gene expression of wild-type, lysine-to-arginine and overexpression mutants of H2A.Z at 0, 30 and 120 minutes during response to caffeine