Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes
| Autor: | Nicolas Derian, Veronika Vlkova, Milan Reiniš, Tomáš Hejhal, Ivan Štěpánek, Martin Sramek, Jana Bieblová, Filip Šenigl, Marie Indrová, Adrien Six, Jana Símová, Veronika Mayerová, David Klatzmann, Veronika Hrušková |
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| Předmět: |
IFNγ signalling
Fibrosarcoma Antigen presentation Down-Regulation Genes MHC Class I Transfection Major histocompatibility complex Epigenesis Genetic Interferon-gamma Mice 5-azacytidine Antigen MHC class I Tumor Cells Cultured Animals Epigenetics Antigen Presentation biology Antigen processing tumour immunology DNA Methylation MHC class I downregulation Up-Regulation Gene Expression Regulation Neoplastic Mice Inbred C57BL DNA demethylation Oncology DNA methylation biology.protein Cancer research Signal Transduction Research Paper |
| Zdroj: | Scopus-Elsevier Europe PubMed Central Oncotarget |
| Popis: | Downregulation of MHC class I expression on tumour cells, a common mechanism by which tumour cells can escape from specific immune responses, can be associated with coordinated silencing of antigen-presenting machinery genes. The expression of these genes can be restored by IFNγ. In this study we documented association of DNA demethylation of selected antigen-presenting machinery genes located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFNγ treatment with MHC class I upregulation on tumour cells in several MHC class I-deficient murine tumour cell lines (TC-1/A9, TRAMP-C2, MK16 and MC15). Our data also documented higher methylation levels in these genes in TC-1/A9 cells, as compared to their parental MHC class I-positive TC-1 cells. IFNγ-mediated DNA demethylation was relatively fast in comparison with demethylation induced by DNA methyltransferase inhibitor 5-azacytidine, and associated with increased histone H3 acetylation in the promoter regions of APM genes. Comparative transcriptome analysis in distinct MHC class I-deficient cell lines upon their treatment with either IFNγ or epigenetic agents revealed that a set of genes, significantly enriched for the antigen presentation pathway, was regulated in the same manner. Our data demonstrate that IFNγ acts as an epigenetic modifier when upregulating the expression of antigen-presenting machinery genes. |
| Databáze: | OpenAIRE |
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