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Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon response
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2012
- Publisher :
- The Rockefeller University Press, 2012.
-
Abstract
- Di-methylation of histone H3 at lysine 9 (H3K9me2) suppresses expression of interferon genes, and deletion or inactivation of the lysine methyltransferase G9a converts fibroblasts into interferon-producing cells resistant to RNA viruses.<br />Effective antiviral immunity depends on the ability of infected cells or cells triggered with virus-derived nucleic acids to produce type I interferon (IFN), which activates transcription of numerous antiviral genes. However, disproportionately strong or chronic IFN expression is a common cause of inflammatory and autoimmune diseases. We describe an epigenetic mechanism that determines cell type–specific differences in IFN and IFN-stimulated gene (ISG) expression in response to exogenous signals. We identify di-methylation of histone H3 at lysine 9 (H3K9me2) as a suppressor of IFN and IFN-inducible antiviral gene expression. We show that levels of H3K9me2 at IFN and ISG correlate inversely with the scope and amplitude of IFN and ISG expression in fibroblasts and dendritic cells. Accordingly, genetic ablation or pharmacological inactivation of lysine methyltransferase G9a, which is essential for the generation of H3K9me2, resulted in phenotypic conversion of fibroblasts into highly potent IFN-producing cells and rendered these cells resistant to pathogenic RNA viruses. In summary, our studies implicate H3K9me2 and enzymes controlling its abundance as key regulators of innate antiviral immunity.
- Subjects :
- Methyltransferase
Immunology
Biology
complex mixtures
Methylation
Epigenesis, Genetic
Histones
03 medical and health sciences
Histone H3
Mice
0302 clinical medicine
Interferon
Transcription (biology)
Gene expression
medicine
Immunology and Allergy
Animals
Epigenetics
Gene
030304 developmental biology
0303 health sciences
Brief Definitive Report
Histone-Lysine N-Methyltransferase
Virology
Immunity, Innate
3. Good health
Cell biology
Mice, Inbred C57BL
Histone
Virus Diseases
030220 oncology & carcinogenesis
biology.protein
bacteria
Interferons
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15409538 and 00221007
- Volume :
- 209
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....5d8ce57af4b7cd3f9f11dd8c1314d758