Mouse embryonic stem cells induce targeted DNA demethylation within human MAGE-A1 transgenes.
(2008) Epigenetics : official journal of the DNA Methylation Society — Vol. 3, n° 1, p. 38-42 (2008)
Files
LORIOT_EPI2008.pdf
Restricted Access - Adobe PDF
- 637.98 KB
Details
- Authors
- Abstract
- 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.
- Affiliations
Citations
Loriot, A., Sterpin, C., De Backer, O., & De Smet, C. (2008). Mouse embryonic stem cells induce targeted DNA demethylation within human MAGE-A1 transgenes. Epigenetics : official journal of the DNA Methylation Society, 3(1), 38-42. https://hdl.handle.net/2078.5/134914 (Original work published 2008)