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Differential regulation of the phosphorylation of Trimethyl-lysine27 histone H3 at serine 28 in distinct populations of striatal projection neurons.
- Source :
-
Neuropharmacology [Neuropharmacology] 2016 Aug; Vol. 107, pp. 89-99. Date of Electronic Publication: 2016 Mar 03. - Publication Year :
- 2016
-
Abstract
- Phosphorylation of histone H3 (H3) on serine 28 (S28) at genomic regions marked by trimethylation of lysine 27 (H3K27me3) often correlates with increased expression of genes normally repressed by Polycomb group proteins (PcG). We show that amphetamine, an addictive psychostimulant, and haloperidol, a typical antipsychotic drug, increase the phosphorylation of H3 at S28 and that this effect occurs in the context of H3K27me3. The increases in H3K27me3S28p occur in distinct populations of projection neurons located in the striatum, the major component of the basal ganglia. Genetic inactivation of the protein phosphatase-1 inhibitor, dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), reduces the phosphorylation of H3K27me3S28 produced by amphetamine and haloperidol. In contrast, knockout of the mitogen- and stress activated kinase 1 (MSK1), which is implicated in the phosphorylation of histone H3, decreases the effect of amphetamine, but not that of haloperidol. Chromatin immunoprecipitation analysis shows that amphetamine and haloperidol increase the phosphorylation of H3K27me3S28 at the promoter regions of Atf3, Npas4 and Lipg, three genes repressed by PcG. These results identify H3K27me3S28p as a potential mediator of the effects exerted by amphetamine and haloperidol, and suggest that these drugs may act by re-activating PcG repressed target genes.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Activating Transcription Factor 3 genetics
Activating Transcription Factor 3 metabolism
Amphetamine pharmacology
Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Central Nervous System Agents pharmacology
Corpus Striatum cytology
Corpus Striatum drug effects
Dopamine and cAMP-Regulated Phosphoprotein 32 metabolism
Epigenesis, Genetic drug effects
Epigenesis, Genetic physiology
Haloperidol pharmacology
Histones genetics
Lipase genetics
Lipase metabolism
Male
Mice, Inbred C57BL
Mice, Transgenic
Neural Pathways cytology
Neural Pathways drug effects
Neural Pathways metabolism
Neurons cytology
Neurons drug effects
Phosphorylation drug effects
Promoter Regions, Genetic drug effects
Promoter Regions, Genetic physiology
Ribosomal Protein S6 Kinases, 90-kDa genetics
Ribosomal Protein S6 Kinases, 90-kDa metabolism
Corpus Striatum metabolism
Histones metabolism
Neurons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 107
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26947946
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2016.02.037