中文摘要
人類的FGL2 gene (又可稱做 fibroleukin和hpT49h) 是在1995年由 Curzio Ruegg所發現，目前對於人類的FGL2 gene的研究並不多。FGL2有prothrombinase的功能，亦有人發現其具有抑制老鼠T 細胞增生和樹突細胞成熟的效用。目前已有報導指出FGL2 在自體和異體移植、特定冠狀病毒所引起的肝臟病變以及細胞激素所造成的流產上扮演重要的角色，但是這些發現都是用豬和老鼠做為模式生物所得的結果。對於人類FGL2 gene的研究並不多。在此，我們著重於人類FGL2 基因的啟動子的探討。
為了探究人類的FGL2 基因的啟動子，我們測試FGL2是否表現在某些人類細胞株，結果發現人類的包皮內皮細胞株(HMEC-1)和Epstein-Barr 病毒感染而癌化的B 細胞在未受刺激的情況下即可表現FGL2，意味著這二種細胞具有能夠調控FGL2啟動子的轉錄因子並適合做為FGL2 啟動子的研究。因此我們將不同長度的人類FGL2啟動子接到的帶螢光報導基因的質體上。將此重組質體送入HMEC-1細胞內，結果發現-135/-1這段區域在啟動子的活性上扮演重要的角色。
另外，我們在HMEC-1細胞觀察到其FGL2可受TNF-α和IL-4誘導而增加的情形，將不同片段FGL2啟動子所構築而成的重組質體送入HMEC-1並經由IL-4刺激，我們發現-135/-1這段區域包含了能受IL-4所調控的DNA片段。進一步，由軟體(TF-SEARCH)和期刋資料中可預測一段STAT6在-135/-1區域中可能為IL-4所調控的標的，若將這含此片段的重組質體突變後，發現其在HMEC-1內喪失受IL-4調控的能力。

Abstract
Human FGL2 is a T lymphocyte-secreted protein that has been reported to possess prothrombinase activity and can inhibit T cell proliferation and maturation in vitro. In mouse, FGL2 is thought to contribute to the pathogenesis of xenograft and allograft rejection, virally induced hepatocellular injury and cytokine induced fetal loss syndrome. Understanding transcription initiation of the human FGL2 gene can enhance our understanding of the biological function of FGL2. Through Q-PCR & RT-PCR, we found that , HMEC-1 (endothelial cell line) and EBV-transformed B cells can constitutively express FGL2. TNF-α and IL-4 can increase FGL2 expression in HMEC-1 cells. Thus, transcriptional regulation of the human FGL2 promoter was analyzed in HMEC-1 cells under conditions of constitutive expression, and under IL-4 induction. By deletion studies, we found that the region that supports constitutive and IL-4 induced FGL2 transcription is located within the nucleotides -135 to -1 upstream of the translation start site of FGL2. Furthermore, the region within -237 to -135 nucleotides may function as a cis negative regulatory DNA element.
Upon IL-4 treatment, FGL2 promoter activity was increased in HMEC-1 cells. This IL-4 responsiveness was abrogated in HMEC-1 cells transiently transfected with human FGL2 promoter that consists of an altered Stat6 binding element located at -87 to -89 relative to ATG start codon.
Three loci of single nucleotide polymorphism (SNP) were identified at position -165, -656, and -1285 within the 5’promoter of the FGL2 gene among Taiwanese individuals. In luciferase reporter assays, the variants -656T & -1285T have the same luciferase activity with -656A & -1285A. The -165C genotype has a lower, though not significant different, basal activity than that of the -165T construct.

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