Epigenetic Regulation of the Placental Fusogenic Protein, Syncytin2
Date Issued
2008
Date
2008
Author(s)
Liang, Ching-Yeu
Abstract
Syncytin 2, an envelope glycoprotein encoded by the human endogenous retrovirus FRD (HERV-FRD), is specifically expressed in placental trophoblasts. It has been reported that syncytin 2 is a fusogenic protein. Therefore, syncytin 2 may play an important role in placental development by regulation of trophoblastic fusion. Previous studies have shown that the placenta exhibits lower overall DNA methylation levels than the embryo. A recent study has shown that the 5’-long terminal repeat (5’LTR) promoter of syncytin 1, which encodes the envelope protein of HERV-W, is hypomehtylated and controls syncytin 1 expression in placenta. n this study, we further investigated whether DNA methylation and histone modification control syncytin 2 expression in placenta. We demonstrated that the 5’LTR of syncytin 2 is hypomethylated and harbors active histone modification in placental cells. In luciferase reporter assay, in vitro DNA methylation inhibited the promoter activity of syncytin 2 5’LTR. Interestingly, the promoter activity of in vitro methylated syncytin 2 5’LTR could be restored in placental cells. To study the mechanism that counteracts the suppressive effect of DNA methylation on syncytin 2 5’LTR promoter in placenta, we demonstrated that placental transcription factor, GCMa, not only regulates syncytin 2 expression but also promotes DNA demethylation on syncytin 2 5’LTR. We further demonstrated that GCMa associates with TDG, an enzyme that involves in DNA demethylation process. This implies that GCMa may recruit TDG to demethylate syncytin 2 5’LTR. Overall, our results reveal an epigenetic regulation of syncytin 2 gene expression and that GCMa is a key factor for DNA demethylation of syncytin 2 promoter and transcription activation of syncytin 2.
Subjects
epigenetics
syncytin
DNA methylation
GCMa
TDG
histone modification
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