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Originally published In Press as doi:10.1074/jbc.M209316200 on October 22, 2002

J. Biol. Chem., Vol. 277, Issue 51, 50062-50068, December 20, 2002
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GCMa Regulates the Syncytin-mediated Trophoblastic Fusion*

Chenchou YuDagger §, Kuofeng Shen§, Meiyao LinDagger , Porchun Chen, Chenchen Lin, Geen-Dong Chang, and Hungwen ChenDagger ||

From the Dagger  Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan and the  Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan

The human placental trophoblast cell can be classified as either a cytotrophoblast or a 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 the 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. To study the placenta-specific fusion mediated by syncytin, we tested whether 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 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 the 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.


* This work was supported by grants from the National Science Council (91-2311-B-001-043) and Academia Sinica, Taiwan (to H. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally to this work.

|| To whom correspondence should be addressed. Tel.: 011-886-2-27855696 ext. 6090; Fax: 011-886-2-27889759; E-mail: hwchen@gate.sinica.edu.tw.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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