p38-Dependent Marking of Inflammatory Genes for Increased NF-kappa B Recruitment

Nat Immunol. 2002 Jan;3(1):69-75. doi: 10.1038/ni748. Epub 2001 Dec 17.

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

  • Acetylation
  • Animals
  • Binding Sites
  • Chemokine CCL2 / genetics*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin / ultrastructure
  • DNA / metabolism
  • Dendritic Cells / metabolism*
  • Dimerization
  • Gene Expression Regulation / physiology*
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Inflammation / genetics*
  • Interleukin-12 / genetics
  • Interleukin-6 / genetics
  • Interleukin-8 / genetics*
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / physiology*
  • Models, Genetic
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Phosphoserine / chemistry
  • Promoter Regions, Genetic*
  • Protamine Kinase / metabolism*
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Structure-Activity Relationship
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Chemokine CCL2
  • Chromatin
  • Histones
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • Phosphoserine
  • Interleukin-12
  • DNA
  • Protamine Kinase
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases