p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment.
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.
Saccani
Simona
S
Institute for Research in Biomedicine, Via Vela 6, CH 6501, Bellinzona, Switzerland.
Pantano
Serafino
S
Natoli
Gioacchino
G
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D018932:Chemokine CCL2 / Q000235:genetics*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D004247:DNA / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D018664:Interleukin-12 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D008957:Models, Genetic; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry; D011401:Promoter Regions, Genetic; D006656:Protamine Kinase / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases
D018932:Chemokine CCL2; D002843:Chromatin; D006657:Histones; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010768:Phosphoserine; D018664:Interleukin-12; D004247:DNA; D006656:Protamine Kinase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases