HLA-G Gene Repression Is Reversed by Demethylation

The HLA-G molecule plays an important role in immune tolerance, protecting the fetus from maternal immune attack, and probably contributes to graft tolerance and tumor escape from the host immune system. HLA-G expression is tightly regulated and involves mechanisms acting in part at the transcriptio...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2003-02, Vol.100 (3), p.1191-1196
Main Authors: Moreau, Philippe, Mouillot, Gaël, Rousseau, Philippe, Marcou, Céline, Dausset, Jean, Carosella, Edgardo D.
Format: Article
Language:English
Subjects:
Antibodies
Azacitidine - analogs & derivatives
Azacitidine - pharmacology
Biological Sciences
Blotting, Southern
Blotting, Western
Cell lines
DNA
DNA Methylation
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Flow Cytometry
Genes
Genetics
Histocompatibility Antigens Class I - biosynthesis
Histocompatibility Antigens Class I - genetics
Histone Deacetylases - pharmacology
HLA Antigens - biosynthesis
HLA Antigens - genetics
HLA-G Antigens
Humans
Immunohistochemistry
Immunology
Messenger RNA
Methylation
Molecular biology
Molecules
Protein synthesis
Repression
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transcription, Genetic
Tumor Cells, Cultured
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Summary:The HLA-G molecule plays an important role in immune tolerance, protecting the fetus from maternal immune attack, and probably contributes to graft tolerance and tumor escape from the host immune system. HLA-G expression is tightly regulated and involves mechanisms acting in part at the transcriptional level. Nevertheless, almost all regulatory sequences that govern constitutive and inducible HLA class I gene transcription are disrupted in the HLA-G gene promoter, suggesting an unusual regulatory process. In further investigating the molecular mechanisms of HLA-G gene activation, we evaluated the influence of epigenetic mechanisms on seven HLA-G-negative cell lines that exhibit various phenotypes. Exposure of cells to histone deacetylase inhibitors, or to the demethylating agent 5-aza-2′-deoxycytidine, revealed that HLA-G gene transcription is inhibited by DNA methylation. Reversal of methylation-mediated repression may directly induce HLA-G cell-surface expression, supporting the idea that HLA-G might be activated by such a mechanism during malignancy, inflammation, and allogenic reactions.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0337539100