AN ALBUMIN ENHANCER LOCATED 10-KB UPSTREAM FUNCTIONS ALONG WITH ITS PROMOTER TO DIRECT EFFICIENT, LIVER-SPECIFIC EXPRESSION IN TRANSGENIC MICE
AN ALBUMIN ENHANCER LOCATED 10-KB UPSTREAM FUNCTIONS ALONG WITH ITS PROMOTER TO DIRECT EFFICIENT, LIVER-SPECIFIC EXPRESSION IN TRANSGENIC MICE
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DOI：
10.1101/gad.1.3.268
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发表时间：
1987-05-01
影响因子：
10.5
通讯作者：
PALMITER, RD
中科院分区：
文献类型：
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作者：
PINKERT, CA;ORNITZ, DM;PALMITER, RD
转基因小鼠被用来定位顺式作用的DNA元件，这些元件对于在成人中高效、组织特异性地表达小鼠白蛋白基因非常重要。测试了长达12kb的小鼠白蛋白5‘-侧翼区与人生长激素(HGH)报告基因融合的嵌合基因。值得注意的是，位于白蛋白启动子上游8.5-10.4千克的区域对于成人肝脏的高水平表达是必不可少的，而在-8.5-0.3kb之间的区域是必不可少的。远上游区域的作用类似于增强子，因为它相对于白蛋白启动子的位置和取向不是关键的；然而，它与异源启动子一起作用不好。在白蛋白基因5‘-侧翼区发现的四个DNA酶敏感位点中，有两个位于远上游和启动子区域；其他可能反映了该基因的发育或环境控制区域。
Transgenic mice were used to locate the cis-acting DNA elements that are important for efficient, tissue-specific expression of the mouse albumin gene in the adult. Chimeric genes with up to 12 kb of mouse albumin 5''-flanking region fused to a human growth homone (hGH) reporter gene were tested. Remarkably, a region located 8.5-10.4 kg upstream of the albumin promoter was essential for high-level expression in adult liver and the region in between -8.5 and -0.3 kb was dispensable. The far-upstream region behaved like an enhancer in that its position and orientation relative to the albumin promoter were not critical; however, it did not function well with a heterologous promoter. Two of four DNase hypersensitive sites found in the 5''-flanking region of the albumin gene map to the far-upstream and promoter regions; the others may reflect regions involved in developmental or environmental control of this gene.