Gene regulation of the human placental fusogenic protein, syncytin

• Main Authors: Kuo-Fang Shen, 沈國芳
• Other Authors: Hungwen Chen
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/65404506306342504073

碩士 === 國立臺灣大學 === 生化科學研究所 === 90 === HERV-W is one of recently identified human endogenous retrovirus and it was found to transcribe three kinds of mRNAs including gag, pol and env. The envelope gene of HERV-W encodes a functional protein that was named as syncytin. Expression of syncytin gene is restricted to placental syncytiotrophoblast. The ability of human cytotrophoblast cells to fuse into syncytiotrophoblast is mediated by syncytin. Therefore, sync- ytin may play an important role in human placental morphogenesis. The transcription factor, GCMa, is highly expressed in the lab-yrinthine trophoblast cells. GCMa is required for placenta develop-ment because genetic ablation of mouse GCMa leads to a failure oflabyrinth layer formation and no fusion of trophoblasts to syncytiot-rophoblasts. In this study, we confirmed that GCMa transcription factor can regulate human syncytin gene in the transient expression assay. Our results also indicated that GCMa protein can bind to thepromoter of syncytin gene by electrophoretic mobility shift assay. We further identified two GCMa binding sites in the promoter regi-on, 25538/25547 and 28026/28033, using DNase I footprinting anal-ysis. In transient expression assay, the transactivation of GCMa on syncytin promoter could not be found when these two GCMa bindi-ng sites were deleted. Overall, we successfully demonstrated that GCMa can regulate human syncytin gene expression and linked thephysiological function of GCMa in the development of syncytiotrop-hoblast to syncytin-mediated fusion.