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Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN- in promyelocytic cells
- Source :
- International Immunology. 20:1457-1466
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
Abstract
- The human promyelocytic cell line THP-1 expresses high level of HLA class II (HLA-II) molecules after IFN-gamma treatment. Here, we report a variant of THP-1 that does not express HLA-II after IFN-gamma. The variant's HLA-II phenotype is constant over time in culture and it is not related to a defective IFN-gamma-signalling pathway. Transfection of CIITA, the HLA-II transcriptional activator, under the control of a cytomegalovirus promoter rescues high level of HLA-DR surface expression in the variant indicating that the biosynthetic block resides in the expression of CIITA and not in the CIITA-dependent transactivation of the HLA-II promoters. Treatment of the variant with 5-azacytidine (5-aza), which inhibits CpG methylation, restores inducibility of HLA-II by IFN-gamma both at transcriptional and phenotypic level and antigen presenting and processing function of the variant. DNA studies demonstrate that the molecular defect of the THP-1 variant originates from the methylation of the CIITA promoter IV. Furthermore, treatment with 5-aza produces a substantial demethylation of CIITA promoter IV and a significant increase of IFN-gamma-dependent HLA-II expression in another myelomonocytic cell line, U937. Therefore hyper-methylation of CIITA promoter IV may be a relevant mechanism of epigenetic control preventing HLA-II IFN-gamma inducibility in the myelomonocytic cell lineage.
- Subjects :
- Transcriptional Activation
Immunology
chemical and pharmacologic phenomena
Biology
Lymphocyte Activation
Interferon-gamma
Transactivation
CIITA
Humans
Immunology and Allergy
Granulocyte Precursor Cells
Epigenetics
Promoter Regions, Genetic
Transcription factor
Regulation of gene expression
Antigen Presentation
Nuclear Proteins
Promoter
HLA-DR Antigens
U937 Cells
General Medicine
Methylation
DNA Methylation
Molecular biology
DNA methylation
Azacitidine
Trans-Activators
Cancer research
Original Research Papers
Subjects
Details
- ISSN :
- 14602377 and 09538178
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- International Immunology
- Accession number :
- edsair.doi.dedup.....af7eebdd7831f06ec5c0fef9da716f5c