casein-kinase-ii and methanesulfonic-acid

The NuA4 complex is a histone H4/H2A acetyltransferase involved in transcription and DNA repair. While histone acetylation is important in many processes, it has become increasingly clear that additional histone modifications also play a crucial interrelated role. To understand how NuA4 action is regulated, we tested various H4 tail peptides harboring known modifications in HAT assays. While dimethylation at arginine 3 (R3M) had little effect on NuA4 activity, phosphorylation of serine 1 (S1P) strongly decreased the ability of the complex to acetylate H4 peptides. However, R3M in combination with S1P alleviates the repression of NuA4 activity. Chromatin from cells treated with DNA damage-inducing agents shows an increase in phosphorylation of serine 1 and a concomitant decrease in H4 acetylation. We found that casein kinase 2 phosphorylates histone H4 and associates with the Rpd3 deacetylase complex, demonstrating a physical connection between phosphorylation of serine 1 and unacetylated H4 tails. Chromatin immunoprecipitation experiments also link local phosphorylation of H4 with its deacetylation, during both transcription and DNA repair. Time course chromatin immunoprecipitation data support a model in which histone H4 phosphorylation occurs after NuA4 action during double-strand break repair at the step of chromatin restoration and deacetylation. These findings demonstrate that H4 phospho-serine 1 regulates chromatin acetylation by the NuA4 complex and that this process is important for normal gene expression and DNA repair.

Topics: Acetylation; Acetyltransferases; Amino Acid Sequence; Casein Kinase II; Chromatin; DNA Damage; DNA Repair; Drug Resistance, Fungal; Histone Acetyltransferases; Histone Deacetylases; Histones; Hydroxyurea; Mesylates; Molecular Sequence Data; Mutation; Peptides; Phosphorylation; Protein Serine-Threonine Kinases; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Serine; Transcription Factors; Transcription, Genetic