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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
V. Vlková, I. Štěpánek, V. Hrušková, F. Šenigl, V. Mayerová, M. Šrámek, J. Šímová, J. Bieblová, M. Indrová, T. Hejhal, N. Dérian, D. Klatzmann, A. Six, M. Reiniš,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NT14461
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
Zdroj
NLK
Free Medical Journals
od 2010
Freely Accessible Journals
od 2010
PubMed Central
od 2010
Europe PubMed Central
od 2010
Open Access Digital Library
od 2010-01-01
PubMed
25071011
DOI
10.18632/oncotarget.2222
Knihovny.cz E-zdroje
- MeSH
- down regulace MeSH
- epigeneze genetická MeSH
- fibrosarkom genetika imunologie metabolismus MeSH
- geny MHC třídy I * MeSH
- interferon gama genetika imunologie metabolismus MeSH
- metylace DNA * MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- prezentace antigenu genetika MeSH
- regulace genové exprese u nádorů MeSH
- signální transdukce MeSH
- transfekce MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
CNRS UMR 7211 Immunology Immunopathology Immunotherapy Paris France
INSERM UMR_S 959 Immunology Immunopathology Immunotherapy Paris France
UPMC Univ Paris 06 UMR 7211 Immunology Immunopathology Immunotherapy Paris France
Citace poskytuje Crossref.org
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