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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References
Kornberg, R. D. & Lorch, Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98, 285–294 (1999).
Grunstein, M. Histone acetylation in chromatin structure and transcription. Nature 389, 349–352 (1997).
Cheung, P., Allis, C. D. & Sassone-Corsi, P. Signaling to chromatin through histone modifications. Cell 103, 263–271 (2000).
Tse, C., Sera, T., Wolffe, A. P. & Hansen, J. C. Disruption of higher-order folding by core histone acetylation dramatically enhances transcription of nucleosomal arrays by RNA polymerase III. Mol. Cell. Biol. 18, 4629–4638 (1998).
Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41–45 (2000).
Dhalluin, C. et al. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399, 491–496 (1999).
Jacobson, R. H., Ladurner, A. G., King, D. S. & Tjian, R. Structure and function of a human TAFII250 double bromodomain module. Science 288, 1422–1425 (2000).
Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).
Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120–124 (2001).
Nakayama, J., Rice, J. C., Strahl, B. D., Allis, C. D. & Grewal, S. I. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292, 110–113 (2001).
Nielsen, S. J. et al. Rb targets histone H3 methylation and HP1 to promoters. Nature 412, 561–565 (2001).
Vandel, L. et al. Transcriptional repression by the retinoblastoma protein through the recruitment of a histone methyltransferase. Mol. Cell. Biol. 21, 6484–6494 (2001).
Hwang, K. K., Eissenberg, J. C. & Worman, H. J. Transcriptional repression of euchromatic genes by Drosophila heterochromatin protein 1 and histone modifiers. Proc. Natl Acad. Sci. USA 98, 11423–11427 (2001).
Jacobs, S. A. et al. Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J. 20, 5232–5241 (2001).
Hendzel, M. J. et al. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106, 348–360 (1997).
Van Hooser, A., Goodrich, D. W., Allis, C. D., Brinkley, B. R. & Mancini, M. A. Histone H3 phosphorylation is required for the initiation, but not maintenance, of mammalian chromosome condensation. J. Cell. Sci. 111, 3497–3506 (1998).
Wei, Y., Yu, L., Bowen, J., Gorovsky, M. A. & Allis, C. D. Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97, 99–109 (1999).
Mahadevan, L. C., Willis, A. C. & Barratt, M. J. Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell 65, 775–783 (1991).
Thomson, S. et al. The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J. 18, 4779–4793 (1999).
Clayton, A. L., Rose, S., Barratt, M. J. & Mahadevan, L. C. Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation. EMBO J. 19, 3714–3726 (2000).
Cheung, P. et al. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol. Cell. 5, 905–915 (2000).
Lo, W. S. et al. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. Mol. Cell. 5, 917–926 (2000).
Nowak, S. J. & Corces, V. G. Phosphorylation of histone H3 correlates with transcriptionally active loci. Genes Dev. 14, 3003–3013 (2000).
Sassone-Corsi, P. et al. Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. Science 285, 886–891 (1999).
Thomson, S., Mahadevan, L. C. & Clayton, A. L. MAP kinase-mediated signalling to nucleosomes and immediate-early gene induction. Semin. Cell. Dev. Biol. 10, 205–214 (1999).
Lo, W. S. et al. Snf1 — a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription. Science 293, 1142–1146 (2001).
Parvin, J. D. & Young, R. A. Regulatory targets in the RNA polymerase II holoenzyme. Curr. Opin. Genet. Dev. 8, 565–570 (1998).
Chadee, D. N. et al. Increased Ser10 phosphorylation of histone H3 in mitogen-stimulated and oncogene-transformed mouse fibroblasts. J. Biol. Chem. 274, 24914–24920 (1999).
English, J. et al. New insights into the control of MAP kinase pathways. Exp. Cell. Res. 253, 255–270 (1999).
Ono, K. & Han, J. The p38 signal transduction pathway: activation and function. Cell Signal. 12, 1–13 (2000).
Davis, R. J. Signal transduction by the JNK group of MAP kinases. Cell 103, 239–252 (2000).
Kyriakis, J. M. & Avruch, J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 81, 807–869 (2001).
DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E. & Karin, M. A cytokine-responsive IκB kinase that activates the transcription factor NF-κB. Nature 388, 548–554 (1997).
Regnier, C. H. et al. Identification and characterization of an IκB kinase. Cell 90, 373–383 (1997).
Karin, M. & Ben-Neriah, Y. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18, 621–663 (2000).
Ghosh, S., May, M. J. & Kopp, E. B. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16, 225–260 (1998).
Baldwin, A. S. Jr The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14, 649–683 (1996).
Saccani, S., Pantano, S. & Natoli, G. Two waves of nuclear factor κB recruitment to target promoters. J. Exp. Med. 193, 1351–1359 (2001).
Weinmann, A. S., Plevy, S. E. & Smale, S. T. Rapid and selective remodeling of a positioned nucleosome during the induction of IL-12 p40 transcription. Immunity 11, 665–675 (1999).
Cella, M., Sallusto, F. & Lanzavecchia, A. Origin, maturation and antigen presenting function of dendritic cells. Curr. Opin. Immunol. 9, 10–16 (1997).
Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).
Langenkamp, A., Messi, M., Lanzavecchia, A. & Sallusto, F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nature Immunol. 1, 311–316 (2000).
Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α. J. Exp. Med. 179, 1109–1118 (1994).
Hecht, A. & Grunstein, M. Mapping DNA interaction sites of chromosomal proteins using immunoprecipitation and polymerase chain reaction. Meth. Enzymol. 304, 399–414 (1999).
Weinmann A. S. et al. Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent event. Nature Immunol. 2, 51–57 (2001).
Alepuz, P. M., Jovanovic, A., Reiser, V. & Ammerer, G. Stress-induced MAP kinase Hog 1 is part of transcription activation complexes. Mol. Cell. 7, 767–777 (2001).
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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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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DOI: https://doi.org/10.1038/ni748
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