Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters - Transcription factor FKHR binds the insulin response sequence
Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters - Transcription factor FKHR binds the insulin response sequence
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DOI：
10.2337/diabetes.48.9.1885
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发表时间：
1999-09-01
期刊：
影响因子：
7.7
通讯作者：
O'Brien, RM
中科院分区：
文献类型：
--
作者：
Ayala, JE;Streeper, RS;O'Brien, RM
由于葡萄糖-6-磷酸酶催化亚单位(G-6-Pase)在1型和2型糖尿病中的过度表达可能导致肝脏葡萄糖产生的特征性增加，我们研究了小鼠G-6-Pase启动子中的胰岛素反应单位(IRU)在人类启动子中是否保守。将一系列人G-6-Pase-氯霉素乙酰转移酶(CAT)融合基因瞬时导入人肝癌细胞系HepG2，观察胰岛素对CAT基础表达的影响。结果表明，在小鼠启动子中发现的IRU在人类启动子中是保守的，但仅在人类启动子中发现的上游多聚体胰岛素反应序列(IRS)基序似乎在功能上是无效的。G-6-Pase IRU由两个不同的启动子区域组成，分别命名为A和B，B区域含有TRs，而A区域作为辅助元件，通过B区域介导胰岛素增强胰岛素对G-6-Pase基因转录的影响。我们以前已经证明了辅助因子结合区A是肝细胞核因子-1，在这里我们证明了叉头蛋白FKHR是胰岛素反应转录因子结合区B的候选者。
Because overexpression of the glucose-6-phosphatase catalytic subunit (G-6-Pase) in both type 1 and type 2 diabetes may contribute to the characteristic increased rate of hepatic glucose production, we have investigated whether the insulin response unit (IRU) identified in the mouse G-6-Pase promoter is conserved in the human promoter. A series of human G-6-Pase-chloramphenicol acetyltransferase (CAT) fusion genes was transiently transfected into human HepG2 hepatoma cells, and the effect of insulin on basal CAT expression was analyzed. The results suggest that the IRU identified in the mouse promoter is conserved in the human promoter, but that an upstream multimerized insulin response sequence (IRS) motif that is only found in the human promoter appears to be functionally inactive. The G-6-Pase IRU comprises two distinct promoter regions, designated A and B, Region B contains an TRS, whereas region A acts as an accessory element to enhance the effect of insulin, mediated through region B, on basal G-6-Pase gene transcription. We have previously shown that the accessory factor binding region A is hepatocyte nuclear factor-1, and we show here that the forkhead protein FKHR is a candidate for the insulin-responsive transcription factor binding region B.