Identification of a novel enhancer sequence in the distal promoter of the rat fatty acid synthase gene
Identification of a novel enhancer sequence in the distal promoter of the rat fatty acid synthase gene
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DOI：
10.1006/bbrc.1999.1034
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发表时间：
1999-08-02
影响因子：
3.1
通讯作者：
Nakamura, MT
中科院分区：
文献类型：
--
作者：
Rufo, C;Gasperikova, D;Nakamura, MT
脂肪酸合酶 (FAS) 基因的近端启动子和第一个内含子含有胰岛素和葡萄糖的响应序列，但这些序列导致的 FAS 启动子活性增加 2 至 3 倍，低于在禁食大鼠中观察到的肝 FAS 基因转录诱导的 20 至 30 倍。使用 DNase I 超敏位点 (HSS) 作图，两个新的肝脏特异性位点定位于以下区域：-8600 至 -8500 (HSS 1) 和 -7300 至 -7000 (HSS 2)，当禁食大鼠喂食葡萄糖时，-7300 至 -7000 区域的 DNase 敏感性增加。当用将-9700和-4606区域与位于-265至+65之间的胰岛素反应区域连接的CAT构建体转染大鼠肝细胞时，FAS启动子活性被诱导15倍。这种增加需要胰岛素和糖皮质激素的存在，删除 HSS 2 消除了 FAS 启动子活性 15 倍的诱导，但删除 HSS 1 则没有效果。显然，肝FAS基因转录的体外调节需要位于-7300至-7000和-265至+65区域的响应元件，(C) 1999学术出版社。
The proximal promoter and first intron of the fatty acid synthase (FAS) gene contains response sequences for insulin and glucose, but the 2- to 3-fold increase in FAS promoter activity attributable to these sequences falls short of the 20- to 30-fold induction in hepatic FAS gene transcription observed in fasted-refed rats. Using DNase I hypersensitivity site (HSS) mapping, two new liver specific sites were localized to the regions of: -8600 to -8500 (HSS 1) and -7300 to -7000 (HSS 2), DNase sensitivity of the -7300 to -7000 region was increased when fasted rats were refed glucose. When rat hepatocytes were transfected with a CAT construct that linked the region of -9700 and -4606 with the insulin response region located between -265 to +65, FAS promoter activity was induced 15-fold. This increase required the presence of both insulin and glucocorticoids, Deleting HSS 2 abolished the 15-fold induction in FAS promoter activity, but removing HSS 1 was without effect. Apparently the in vitro regulation of hepatic FAS gene transcription requires response elements located in the region of -7300 to -7000 and -265 to +65, (C) 1999 Academic Press.