Mouse embryonic stem cells induce targeted DNA demethylation within human MAGE-A1 transgenes

Axelle Loriot , Christiane Sterpin , Olivier De Backer and Charles De Smet

volume 3 | issue 1

January/February 2008
Pages: 38 - 42

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Human tumor development is often associated with a DNA demethylation process. This results in the activation of germline-specific genes, such as MAGE-A1, which rely on DNA methylation for repression in somatic tissues. Here, we searched to identify a cell line possessing ongoing DNA demethylation activity targeted to MAGE-A1. We first assessed MAGE-A1-expressing human tumor cell lines, by evaluating their ability to induce demethylation of MAGE-A1 transgenes that were methylated in vitro before transfection. All cell lines lacked such activity, suggesting that MAGE-A1 hypomethylation in tumors results from a past demethylation event. We then turned to mouse embryonic stem (mES) cells, which are characterized by a high level of methylation plasticity. Interestingly, in vitro methylated MAGE-A1 transgenes became demethylated after transfection into mES cells. Demethylation was targeted to the 5’-region of MAGE-A1, and was strongly reduced at mutated MAGE-A1 transgenes exhibiting impaired promoter activity. Our results indicate that mES cells induce demethylation of MAGE-A1, and represent therefore a valuable system to study this tumor-related process.

Authors

Axelle Loriot

Research Unit for Tropical Diseases, de Duve Institute, UniversitÃ© catholique de Louvain

Christiane Sterpin

FUNDP University of Namur

Olivier De Backer