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Papers In Press, published online ahead of print October 22, 2002
Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115
Corresponding Author: hwchen{at}gate.sinica.edu.tw
The human placental trophoblast cell can be classified into cytotrophoblast and syncytiotrophoblast. Cytotrophoblasts can function as stem cells for the development of the syncytiotrophoblast layer via cell fusion. An envelope gene of the human endogenous retrovirus family W (HERV-W) called syncytin is specifically expressed in the syncytiotrophoblast layer. Syncytin is a fusogenic membrane protein, therefore it can mediate fusion of cytotrophoblasts into the syncytiotrophoblast layer, which is essential for pregnancy maintenance. GCMa is a placenta-specific transcription factor and is required for placental development. In order to study the placenta-specific fusion mediated by syncytin, we tested if GCMa is involved in this process by regulating syncytin gene expression. In this report, we demonstrate that GCMa was able to regulate syncytin gene expression via two GCMa-binding sites upstream of the 5’-long terminal repeat of the syncytin-harboring HERV-W family member in BeWo and JEG3 cells but not in HeLa cells. Furthermore, adenovirus-directed expression of GCMa enhanced syncytin gene expression and the syncytin-mediated cell fusion in BeWo and JEG3 cells but not in HeLa cells. Therefore, the integration site of the syncytin-harboring HERV-W family member in the human genome is close to functional GCMa-binding sites by which GCMa can specifically transactivate syncytin gene expression in trophoblast cells. Our results may help to explain the mechanism underlying the cell fusion event specific for syncytiotrophoblast formation.
J. Biol. Chem, 10.1074/jbc.M209316200
Submitted on September 11, 2002
Revised on October 21, 2002
Accepted on October 22, 2002
GCMa regulates the syncytin-mediated trophoblastic fusion
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