HLA-G gene repression is reversed by demethylation

被引:136
作者
Moreau, P
Mouillot, G
Rousseau, P
Marcou, C
Dausset, J
Carosella, ED
机构
[1] Hop St Louis, Inst Univ Hematol, CEA,Serv Rech Hamatoimmunol, Direct Sci Vivant,Dept Rech Med, F-75010 Paris, France
[2] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, F-75010 Paris, France
关键词
D O I
10.1073/pnas.0337539100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1191 / 1196
页数:6
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