Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-γ in promyelocytic cells

Andrea De Lerma Barbaro, Alessandro De Ambrosis, Barbara Banelli, Giuseppina Li Pira, Ottavia Aresu, Massimo Romani, Silvano Ferrini, Roberto S. Accolla

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The human promyelocytic cell line THP-1 expresses high level of HLA class II (HLA-II) molecules after IFN-γ treatment. Here, we report a variant of THP-1 that does not express HLA-II after IFN-γ. The variant's HLA-II phenotype is constant over time in culture and it is not related to a defective IFN-γ-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-γ 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-γ-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-γ inducibility in the myelomonocytic cell lineage.

Original languageEnglish
Pages (from-to)1457-1466
Number of pages10
JournalInternational Immunology
Volume20
Issue number11
DOIs
Publication statusPublished - 2008

Fingerprint

Methylation
Azacitidine
Cell Line
Antigen Presentation
HLA-DR Antigens
Cell Lineage
Cytomegalovirus
Epigenomics
Transcriptional Activation
Transfection
Phenotype
DNA

Keywords

  • 5-azacytidine
  • Gene regulation
  • MHC class II
  • Transcription factors

ASJC Scopus subject areas

  • Immunology

Cite this

Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-γ in promyelocytic cells. / De Lerma Barbaro, Andrea; De Ambrosis, Alessandro; Banelli, Barbara; Pira, Giuseppina Li; Aresu, Ottavia; Romani, Massimo; Ferrini, Silvano; Accolla, Roberto S.

In: International Immunology, Vol. 20, No. 11, 2008, p. 1457-1466.

Research output: Contribution to journalArticle

De Lerma Barbaro, A, De Ambrosis, A, Banelli, B, Pira, GL, Aresu, O, Romani, M, Ferrini, S & Accolla, RS 2008, 'Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-γ in promyelocytic cells', International Immunology, vol. 20, no. 11, pp. 1457-1466. https://doi.org/10.1093/intimm/dxn103
De Lerma Barbaro, Andrea ; De Ambrosis, Alessandro ; Banelli, Barbara ; Pira, Giuseppina Li ; Aresu, Ottavia ; Romani, Massimo ; Ferrini, Silvano ; Accolla, Roberto S. / Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-γ in promyelocytic cells. In: International Immunology. 2008 ; Vol. 20, No. 11. pp. 1457-1466.
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