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研究生:洪振家
研究生(外文):Chen-Chia Hung
論文名稱:USF1與Rta參與Epstein-BarrvirusBRLF1啟動子的活化
論文名稱(外文):Activation of the Epstein-Barr virus BRLF1 promoter by USF1 and Rta
指導教授:劉世東
指導教授(外文):S. T. Liu
學位類別:碩士
校院名稱:長庚大學
系所名稱:基礎醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
論文頁數:48
中文關鍵詞:USF1EBVRtaBRLF1
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Epstein-Barr virus (EB病毒)極早期蛋白質Rta的表現受到BRLF1啟動子 (Rp)的的調控,當Rta表現後將活化EB病毒進入溶裂循環,並影響下游早期及晚期基因的表現,因此,研究Rp的調控機制將有助於了解EB病毒潛伏循環與溶裂循環的轉換。由DNA序列分析顯示, Rp含有5個可能會受到USF1調控的E-box序列。首先以不同Rp刪除株及突變株報導質體分析USF1對Rp活性的影響,結果發現位於Rp -84至-79區域的E-box序列 (5’-CATGTG)對於USF1調控Rp活性很重要。進一步以electrophoretic mobility shift assay (EMSA), DNA affinity precipitation assay (DAPA)及chromatin immunoprecipitation (ChIP)分別證實USF1能結合在此E-box序列上以促進Rta的表現。本研究也以GST pull-down及免疫沉澱法證明Rta可以與USF1結合形成複合體,再以DAPA發現Rta能透過USF1與Rp -84至-79區域的E-box序列結合。更進一步發現Rta與USF1有共同活化Rp的能力,因此推測Rta也可能透過E-box及USF1活化自身啟動子活性。綜合以上所述,本研究發現Rp -84至-79區域的E-box為USF1結合序列,而Rta可以藉由與USF1形成複合體的方式透過USF1結合序列進行自我活化。
Rta is a transcription factor expressed by the Epstein-Barr virus (EBV) during the immediate-early stage of the lytic cycle. This investigation finds that the promoter that transcribes the Rta gene, BRLF1, contains five putative E-Box sequences. Deletion and transient transfection analysis revealed that only the proximal E-Box (5’-CATGTG) located at between -84 and -79 is critical to the activation of the BRLF1 promoter by USF1. The binding of USF1 to this E-box sequence was confirmed by elelctrophoretic mobility shift assay (EMSA), DNA-affinity precipitation assay (DAPA)and chromatin immunoprecipitation (ChIP). Moreover, GST pull-down and immunoprecipitation demonstrated that USF1 forms a complex with Rta on this USF-1 binding site on Rp. The binding appears to autoregulate the transcription of BRLF1. The results from this study reveal how the transcription of BRLF1 is regulated by USF1 and Rta.
指導教授推薦書…………………………………………………………………
口試委員會審定書………………………………………………………………
授權書……………………………………………………………………………iii
誌謝……………………………………………………………………………….iv
中文摘要…………………………………………………………………………..v
英文摘要………………………………………………………………………….vii
目錄………………………………………………………………………………..ix
中文摘要..…………………………………………………………………………. 1
英文摘要……………………………………………………………………………2
緒論…………………………………………………………………………………3
本研究計畫之目的…………………………………………………………………11
材料與方法…………………………………………………………………………12
研究結果…………………………………………………………………………….21
討論………………………………………………………………………………….35
參考文獻…………………………………………………………………………… 39
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