Glutamate induces histone H3 phosphorylation but not acetylation in striatal neurons: role of mitogen- and stress-activated kinase-1.
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.
Brami-Cherrier
Karen
K
Université Pierre et Marie Curie-Paris 6, Paris, France, and CNRS, UMR 7102, Paris, France.
Lavaur
Jeremie
J
Pagès
Christiane
C
Arthur
J Simon C
JS
Caboche
Jocelyne
J
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000172:deficiency / Q000502:physiology*; D048055:Mitogen-Activated Protein Kinase 8 / Q000172:deficiency / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D015533:Transcriptional Activation
D004791:Enzyme Inhibitors; D006657:Histones; D018698:Glutamic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048055:Mitogen-Activated Protein Kinase 8