title: GCMa regulates the syncytin-mediated trophoblastic fusion.
abstract: 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.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Chenchou
authors.initials: C
authors.lastname: Yu
authors.forename: Kuofeng
authors.initials: K
authors.lastname: Shen
authors.forename: Meiyao
authors.initials: M
authors.lastname: Lin
authors.forename: Porchun
authors.initials: P
authors.lastname: Chen
authors.forename: Chenchen
authors.initials: C
authors.lastname: Lin
authors.forename: Geen-Dong
authors.initials: GD
authors.lastname: Chang
authors.forename: Hungwen
authors.initials: H
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D005786:Gene Expression Regulation; D015723:Gene Library; D015686:Gene Products, env / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D007313:Insecta; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D010920:Placenta / Q000378:metabolism*; D011233:Precipitin Tests; D011257:Pregnancy Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D015686:Gene Products, env; D009479:Neuropeptides; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; C405335:syncytin; D015500:Chloramphenicol O-Acetyltransferase; D003850:Deoxyribonuclease I