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p38-dependent marking of inflammatory genes for increased NF-κB recruitment

Nature Immunology volume 3, pages 69–75 (2002)Cite this article

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-κB binding sites contained in H3 phosphorylated promoters, which indicated that p38-dependent H3 phosphorylation may mark promoters for increased NF-κB recruitment. These results show that p38 plays an additional role in the induction of the inflammatory and immune response: the regulation of NF-κB recruitment to selected chromatin targets.

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Figure 1: Microbial products and CD40L induce phosphorylation and phosphoacetylation of histone H3 in primary human monocyte–derived DCs.
Figure 2: H3 phosphorylation and phosphoacetylation triggered by inflammatory stimuli occur through a p38-dependent pathway.
Figure 3: Phosphorylation of histone H3 occurs on a subset of LPS-induced cytokine and chemokine genes.
Figure 4: p38 activation is required for NF-κB recruitment to promoters undergoing H3 phosphorylation.
Figure 5: The intensity and duration of p38 activation in response to different agonists influences the NF-κB response.
Figure 6: The IκBα promoter undergoes a rapid and p38-independent H3 phosphorylation.

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Acknowledgements

We thank A. Lanzavecchia, M. Molinari, F. Sallusto, M. Thelen, R. Gherzi and M. Karin for useful comments on the manuscript and members of F. Sallusto's lab for help with DC culture and analysis.

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  1. Institute for Research in Biomedicine, Via Vela 6, Bellinzona, CH 6501, Switzerland

    Simona Saccani, Serafino Pantano & Gioacchino Natoli

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  1. Simona Saccani
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Correspondence to Gioacchino Natoli.

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Saccani, S., Pantano, S. & Natoli, G. p38-dependent marking of inflammatory genes for increased NF-κB recruitment. Nat Immunol 3, 69–75 (2002). https://doi.org/10.1038/ni748

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