Epigenetic regulations in the IFN signalling pathway: IFN-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes [TC1A9_IFN]

Reversible MHC class I deficiency on tumour cells is commonly caused by coordinated silencing of antigen-presenting machinery genes and restorable by IFN. Here we describe association of DNA demethylation of selected antigen-presenting machinery gene regulatory regions located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFN treatment with MHC class I upregulation on tumour cells. Our novel findings demonstrate that IFN acts as an epigenetic modifier upregulating the expression of antigen-presenting machinery genes through DNA demethylation. Our data also cast more light on the role of DNA methylation in tumour cell escape from specific immunity.

6

Vlková V, Štěpánek I, Hrušková V, Šenigl F, Mayerová V, Šrámek M, Šímová J, Bieblová J, Indrová M, Hejhal T, Dérian N, Klatzmann D, Six A, Reiniš M