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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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 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.[1]


  1. HLA-G gene repression is reversed by demethylation. Moreau, P., Mouillot, G., Rousseau, P., Marcou, C., Dausset, J., Carosella, E.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
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