Glutamate induces histone H3 phosphorylation but not acetylation in striatal neurons: role of mitogen- and stress-activated kinase-1.

摘要: Chromatin remodelling is thought to play a key role in gene regulation that underlies long-term synaptic plasticity and memory formation. The dynamic process of chromatin requires post-translational modifications histones, group highly basic proteins are tightly linked DNA. In the present study, we investigated histone H3 response glutamate stimulation leading c-Fos c-Jun induction an vitro model system striatal neurons culture. Intracellular signalling pathways implicated these were analysed. Histone acetylation was strong basal conditions unmodified by treatment. By contrast, induced phosphorylation inhibited selective inhibitors extracellular signal-regulated kinase (ERK) p38 mitogen-activated protein (p38 MAPK) pathways, U0126 SB203580, respectively. Blocking activation mitogen- stress-activated 1 (MSK1), downstream ERK MAPK, pharmacological approach or using cells from MSK1 deficient mice, totally abolished phosphorylation, as well induction. immunoprecipitation assays confirmed increased levels phosphorylated at c-jun promoter. Altogether, our data highlight crucial nucleosomal necessary for neuronal cells.