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A single element of the elastase I enhancer is sufficient to direct transcription selectively to the pancreas and gut.

机译:弹性蛋白酶I增强子的单个元件足以选择性地将转录引导至胰腺和肠。

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摘要

The elastase I (EI) gene is expressed at high levels in the exocrine pancreas and at lower levels in other regions of the gut. The transcriptional enhancer of the EI gene, from nucleotides -205 to -72, recapitulates the expression of the endogenous gene in transgenic mice; it directs not only pancreatic acinar cell expression of a human growth hormone (hGH) transgene but also expression to the stomach, duodenum, and colon. This pattern of selective expression limited to the gastroenteropancreatic organ system is specified by the A element, one of three functional elements in the EI enhancer. When multimerized, the A element directed expression of a hGH reporter gene selectively to the pancreas, stomach, and intestine in transgenic mice. Immunofluorescent localization of hGH indicated that the A element multimer transgenes were expressed in the acinar cells of the pancreas as well as in Brunner's gland cells of the duodenum. The A element binds a pancreatic acinar cell-specific factor, PTF1. Our results show that while the A element is responsible for directing tissue and cell type specificity, other elements of the enhancer must be involved in the regulation of the level of gene expression.
机译:弹性蛋白酶I(EI)基因在外分泌胰腺中高水平表达,在肠道其他区域则低水平表达。 EI基因的转录增强子(从-205到-72核苷酸)概括了转基因小鼠中内源基因的表达。它不仅指导人类生长激素(hGH)转基因的胰腺腺泡细胞表达,而且还指导胃,十二指肠和结肠的表达。限于胃肠胰器官系统的这种选择性表达模式由EI增强子中三个功能性元素之一的A元素指定。当被多聚化时,在转基因小鼠中,A元件将hGH报告基因的表达选择性地导向胰腺,胃和肠。 hGH的免疫荧光定位表明A元素多聚体转基因在胰腺的腺泡细胞以及十二指肠的Brunner腺细胞中表达。 A元素结合胰腺腺泡细胞特异性因子PTF1。我们的结果表明,尽管A元素负责指导组织和细胞类型的特异性,但增强子的其他元素也必须参与基因表达水平的调节。

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