Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation

The induction of immediate-early (IE) genes, including proto-oncogenes c-fo s and c-jun, correlates well with a nucleosomal response, the phosphorylati on of histone H3 and HMG-14 mediated via extracellular signal regulated kin ase or p38 MAP kinase cascades, Phosphorylation is targeted to a minute fra ction of histone H3, which is also especially susceptible to hyperacetylati on. Here, we provide direct evidence that phosphorylation and acetylation o f histone H3 occur on the same histone H3 tail on nucleosomes associated wi th active IE gene chromatin. Chromatin immunoprecipitation (ChIP) assays we re performed using antibodies that specifically recognize the doubly-modifi ed phosphoacetylated form of histone H3, Analysis of the associated DNA sho ws that histone H3 on c-fos- and c-jun-associated nucleosomes becomes doubl y-modified, the same H3 tails becoming both phosphorylated and acetylated, only upon gene activation. This study reveals potential complications of oc clusion when using site-specific antibodies against modified histones, and shows also that phosphorylated H3 is more sensitive to trichostatin A (TSA) -induced hyperacetylation than non-phosphorylated H3, Because MAP kinase-me diated gene induction is implicated in controlling diverse biological proce sses, histone H3 phosphoacetylation is likely to be of widespread significa nce.