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J. Biol. Chem., Vol. 277, Issue 51, 50062-50068, December 20, 2002
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From the 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.
GCMa Regulates the Syncytin-mediated Trophoblastic Fusion*
§,
,
¶
Institute of Biological Chemistry, Academia
Sinica, Nankang, Taipei 115, Taiwan and the ¶ Graduate Institute
of Biochemical Sciences, National Taiwan University,
Taipei 106, Taiwan
*
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.
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.
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