Abstract
We found that inflammatory stimuli induce p38 mitogen-activated protein kinase-dependent phosphorylation and phosphoacetylation of histone H3; this selectively occurred on the promoters of a subset of stimulus-induced cytokine and chemokine genes. p38 activity was required to enhance the accessibility of the cryptic NF-kappa B binding sites contained in H3 phosphorylated promoters, which indicated that p38-dependent H3 phosphorylation may mark promoters for increased NF-kappa B recruitment. These results show that p38 plays an additional role in the induction of the inflammatory and immune response: the regulation of NF-kappa B recruitment to selected chromatin targets.
MeSH terms
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Acetylation
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Animals
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Binding Sites
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Chemokine CCL2 / genetics*
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Chromatin / genetics
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Chromatin / metabolism*
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Chromatin / ultrastructure
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DNA / metabolism
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Dendritic Cells / metabolism*
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Dimerization
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Gene Expression Regulation / physiology*
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Histones / chemistry
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Histones / metabolism*
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Humans
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Inflammation / genetics*
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Interleukin-12 / genetics
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Interleukin-6 / genetics
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Interleukin-8 / genetics*
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Lipopolysaccharides / pharmacology
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MAP Kinase Signaling System / physiology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / physiology*
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Models, Genetic
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NF-kappa B / metabolism*
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Phosphorylation
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Phosphoserine / chemistry
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Promoter Regions, Genetic*
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Protamine Kinase / metabolism*
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Protein Binding
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Protein Processing, Post-Translational*
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Structure-Activity Relationship
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Transcription, Genetic
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p38 Mitogen-Activated Protein Kinases
Substances
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Chemokine CCL2
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Chromatin
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Histones
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Interleukin-6
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Interleukin-8
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Lipopolysaccharides
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NF-kappa B
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Phosphoserine
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Interleukin-12
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DNA
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Protamine Kinase
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases