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

Karen Brami-Cherrier, Jeremie Lavaur, Christiane Pagès, J. Simon C. Arthur, Jocelyne Caboche

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


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

Original languageEnglish
Pages (from-to)697-708
Number of pages12
JournalJournal of Neurochemistry
Issue number3
Early online date23 Nov 2006
Publication statusPublished - May 2007


  • Chromatin immunoprecipitation
  • Extracellular signal-regulated kinase and p38mitogen-activated protein kinase
  • Glutamate
  • Histone H3
  • Immediate early gene
  • Mitogen and stress-activated kinase-1
  • Striatal neurons


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