Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/21848
標題: CABYR基因之調控
Regulation of the CABYR gene
作者: 鍾瑋敏
Chung, Wei-Mimg
關鍵字: CABYR
CABYR
PBMC
白血球
出版社: 分子生物學研究所
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摘要: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is classified as a cancer-testis antigen, a category of cancer antigens whose expression in normal tissues is primarily restricted to male germ cells in the testis but not in adult somatic tissues. Recently, it has been suggested that this protein may play a role during brain development based on the observation that CABYR transcripts are differentially expressed in both fetal and adult brains. Studies on CABYR are very limited. Previous work of this laboratory found that CABYR transcripts are also detected in human leukocytes. To identify the cell type(s) expressing CABYR, RT-PCR and Western blot analysis were performed using total RNA and cell lysates, respectively, isolated from monocytes, lymphocytes and polymorphonuclear cells (PMN). The results showed that CABYR is expressed in lymphocytes and monocytes but not in the PMNs, suggesting that CABYR may play a role in acquired immune response. To underestand the mechanism responsible for the differential regulation of CABYR gene expression, the promoter activity of the 1-kb DNA fragment upstream of the start codon (designated +1) was analyzed in both CABYR positive and negative cells. For this purpose, a promoter-probing reporter plasmid, pEGFP-N1-CABYR-promoter, was constructed by cloning the above DNA fragment upstream of the EGFP coding region. pEGFP-N1-CABYR-promoter was transfected into lymphocytes, monocytes, and PMNs. Cells expressing GFP were found in all three transfected cell types indicating that the trans-factors required for the CABYR gene expression are present in these three cell types. Next, the effect of DNA methylation on the promoter activity was investigated because CpG islands were present in the 1-kb DNA fragment. Three luciferase expression plasmids, pGL3-luci1, pGL3-luci2 and pGL3-luci3 driven by the upstream regions encompassing -1 to -1075, -1 to -700, -1 to -300, respectively, relative to the start codon were constructed and subjected to in vitro methylation. 293T cells were transfected with either the methylated or unmethylated plasmids. The luciferase activities of cells transfected with the unmethylated plasmids were found to correlated with the length of the promoter regions. In contrast, very low activities were detected in the cells transfected with the methylated plasmids. Together, the results suggested that methylation on the promoter region may be one of the mechanisms that regulates the expression of CABYR. The methylation status of CABYR in lymphocyte and PMN in vivo deserves further investigation.
Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) 目前被認定為cancer-testis antigen,cancer-testis antigen主要表現在正常人睪丸的精細胞,而體細胞則不會表現。近來研究結果發現在成人腦細胞和嬰兒腦細胞中CABYR會表現不同的variants,因此認為CABYR可能與腦細胞的發育有關。目前為止對CABYR的相關研究有限,先前本實驗室發現在人體正常的白血球細胞中會表現CABYR。爲了觀察在哪一類的白血球細胞中會表現CABYR,將monocytes, lymphocytes和polymorphonuclear cells (PMN) 分離後,利用total RNA和cell lysates進行 RT-PCR以及Western blotting分析,結果顯示lymphocytes和monocytes會表現CABYR, PMN則不會表現CABYR,因此CABYR可能參與acquired immune response。為了瞭解CABYR gene之調控機制,分析CABYR positive 和 negative 細胞 之CABYR 基因轉錄起始點1-kb 之DNA片段。首先將此段約1-kb DNA構築於帶有螢光基因的質體,得pEGFP-N1-CABYR-promoter。再將pEGFP-N1-CABYR-promoter 轉染到monocytes、lymphocytes和PMNs,發現三種細胞都有螢光表現,顯示細胞內都含有調控CABYR 啟動子的調控因子。CABYR啟動子分析的結果得知其含有CpG islands,因此接著觀察DNA甲基化是否影響此1-kb 之CABYR啟動子的活性。構築三段帶有不同長度CABYR 啟動子序列的載體,分別為pGL3-luci1、pGL3-luci2、pGL3-luci3,長度分別取自轉錄起始點上游區域之 -1 to -1075、-1 to -700、-1 to -300,並將質體進行 in vitro甲基化。將甲基化和未甲基化的質體轉染到293T細胞內,細胞經轉染甲基化和未甲基化的質體所表現之Luciferase活性與啟動子之長度有相對關係。然而,DNA經過酵素甲基化後luciferase活性有顯著的降低。根據以上的實驗結果可得知CABYR基因在細胞中的調控可能受到甲基化的影響。對於lymphocytes和PMNs之CABYR 啟動子甲基化位置則留待未來進一步的探討。
URI: http://hdl.handle.net/11455/21848
其他識別: U0005-1708200718201600
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1708200718201600
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