Control of proinflammatory gene programs by regulated trimethylation and demethylation of histone H4K20
- PMID: 22921934
- PMCID: PMC3472359
- DOI: 10.1016/j.molcel.2012.07.020
Control of proinflammatory gene programs by regulated trimethylation and demethylation of histone H4K20
Abstract
Regulation of genes that initiate and amplify inflammatory programs of gene expression is achieved by signal-dependent exchange of coregulator complexes that function to read, write, and erase specific histone modifications linked to transcriptional activation or repression. Here, we provide evidence for the role of trimethylated histone H4 lysine 20 (H4K20me3) as a repression checkpoint that restricts expression of toll-like receptor 4 (TLR4) target genes in macrophages. H4K20me3 is deposited at the promoters of a subset of these genes by the SMYD5 histone methyltransferase through its association with NCoR corepressor complexes. Signal-dependent erasure of H4K20me3 is required for effective gene activation and is achieved by NF-κB-dependent delivery of the histone demethylase PHF2. Liver X receptors antagonize TLR4-dependent gene activation by maintaining NCoR/SMYD5-mediated repression. These findings reveal a histone H4K20 trimethylation/demethylation strategy that integrates positive and negative signaling inputs that control immunity and homeostasis.
Copyright © 2012 Elsevier Inc. All rights reserved.
Figures
Similar articles
-
The novel methyltransferase SETD4 regulates TLR agonist-induced expression of cytokines through methylation of lysine 4 at histone 3 in macrophages.Mol Immunol. 2019 Oct;114:179-188. doi: 10.1016/j.molimm.2019.07.011. Epub 2019 Jul 31. Mol Immunol. 2019. PMID: 31376731
-
SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation.Epigenetics Chromatin. 2017 Feb 23;10:8. doi: 10.1186/s13072-017-0115-7. eCollection 2017. Epigenetics Chromatin. 2017. PMID: 28250819 Free PMC article.
-
Histone methylation modifiers in cellular signaling pathways.Cell Mol Life Sci. 2015 Dec;72(23):4577-92. doi: 10.1007/s00018-015-2023-y. Epub 2015 Aug 25. Cell Mol Life Sci. 2015. PMID: 26305020 Free PMC article. Review.
-
Mechanisms establishing TLR4-responsive activation states of inflammatory response genes.PLoS Genet. 2011 Dec;7(12):e1002401. doi: 10.1371/journal.pgen.1002401. Epub 2011 Dec 8. PLoS Genet. 2011. PMID: 22174696 Free PMC article.
-
Decoding the histone H4 lysine 20 methylation mark.Crit Rev Biochem Mol Biol. 2010 Oct;45(5):440-52. doi: 10.3109/10409238.2010.504700. Crit Rev Biochem Mol Biol. 2010. PMID: 20735237 Review.
Cited by
-
Negative regulation of SH2B3 by SMYD5 controls epithelial-mesenchymal transition in lung cancer.Mol Cells. 2024 May;47(5):100067. doi: 10.1016/j.mocell.2024.100067. Epub 2024 May 7. Mol Cells. 2024. PMID: 38723947 Free PMC article.
-
The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.Int J Mol Sci. 2024 Feb 27;25(5):2750. doi: 10.3390/ijms25052750. Int J Mol Sci. 2024. PMID: 38473997 Free PMC article. Review.
-
Epigenetic regulation of innate immune dynamics during inflammation.J Leukoc Biol. 2024 Mar 29;115(4):589-606. doi: 10.1093/jleuko/qiae026. J Leukoc Biol. 2024. PMID: 38301269 Free PMC article. Review.
-
The Role of Protein Methyltransferases in Immunity.Molecules. 2024 Jan 11;29(2):360. doi: 10.3390/molecules29020360. Molecules. 2024. PMID: 38257273 Free PMC article. Review.
-
Placental transcriptomic signatures of prenatal and preconceptional maternal stress.Mol Psychiatry. 2024 Apr;29(4):1179-1191. doi: 10.1038/s41380-023-02403-6. Epub 2024 Jan 11. Mol Psychiatry. 2024. PMID: 38212375 Free PMC article.
References
-
- Abramoff MD, Magalhaes PJ, Ram SJ. Image Processing with ImageJ. Biophotonics International. 2004;11:36–42.
-
- Albert M, Helin K. Histone methyltransferases in cancer. Semin Cell Dev Biol. 2010;21:209–220. - PubMed
-
- Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129:823–837. - PubMed
-
- Blaschke F, Takata Y, Caglayan E, Collins A, Tontonoz P, Hsueh WA, Tangirala RK. A nuclear receptor corepressor-dependent pathway mediates suppression of cytokine-induced C-reactive protein gene expression by liver X receptor. Circ Res. 2006;99:e88–99. - PubMed
-
- Boutros M, Kiger AA, Armknecht S, Kerr K, Hild M, Koch B, Haas SA, Paro R, Perrimon N. Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science. 2004;303:832–835. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases