本論文之目的為探討人類嗜酸性白血球神經毒素(EDN)及嗜酸性白血球陽離子蛋白(ECP)之啟動子活性調控機制。EDN及ECP為人類核醣核酸水解酶(RNase)之成員，其基因(edn, rnase2; ecp, rnase3)位於第14號染色體長臂第二區第四條帶和第3區第四條帶之間。本論文運用生物資訊、分子生物學、及細胞生物學等實驗方法，首先報導靈長類動物中edn及ecp啟動子的序列及其差異。鑒於ecp係由新世界猴演化至舊世界猴世代時由edn基因複製產生，比對彼此啟動子序列發現一段34個鹼基(34-nt)區域的差異。由於此段序列僅保留於靈長類的edn與舊世界猴的ecp之啟動子中，因此推斷此34-nt區域在舊世界猴演化至類人類猿世代時發生基因刪除的現象。由啟動子活性分析檢測得知，包含此34-nt區域使得edn的轉錄功能高於ecp，亦可選殖加入ecp啟動子序列中以加強其轉錄能力。本研究發現轉錄因子MAZ及Sp1會與34-nt序列結合影響起動子活性，更進一步證明MAZ與Sp1具備反式調控的作用，MAZ具有抑制edn啟動子之轉錄活性，而Sp1則具有增強啟動子的活性。除了34-nt區域以外，啟動子中−350/−329(ednR2)區域對於edn的轉錄活性亦非常重要，變異後會降低啟動子基因活性。依據本實驗室先前的研究發現HNF4轉錄因子在試管中及細胞內均會與ednR2結合，但過量表現HNF4卻會降低edn之轉錄作用。究其原因如下：表現過多的HNF4與edn啟動子競爭結合在34-nt區域之Sp1，進而阻礙Sp1與DNA的結合而抑制其轉錄活化能力。總而言之，本研究發現靈長類動物在演化過程中，34-nt區域被保留於edn基因中，34-nt與ednR2的共同調控為造成edn和ecp基因在肝臟細胞中表現量不同的原因之ㄧ。本論文首先發現調控edn表現的新穎機制，係由MAZ及Sp1兩轉錄因子透過競爭相同結合部位而產生調控活性。此外， HNF4轉錄因子，微量時經ednR2活化edn的表現，過量時則會抑制edn基因的表現。本研究對於在肝臟細胞中edn表現量遠高於ecp提出新的見解，具體貢獻於嗜酸性白血球核醣核酸水解酶的基因調控功能之研究領域。

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