A beta-cell-specific protein binds to the two major regulatory sequences of the insulin gene enhancer.
A beta-cell-specific protein binds to the two major regulatory sequences of the insulin gene enhancer.
复制标题
β细胞特异性蛋白质与胰岛素基因增强子的两个主要调节序列结合。
DOI：
10.1073/pnas.85.12.4228
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发表时间：
1988
影响因子：
11.1
通讯作者：
T. Edlund
中科院分区：
文献类型：
--
作者：
H. Ohlsson;O. Karlsson;T. Edlund
大鼠胰岛素1基因的选择性转录主要依赖于位于5'侧翼DNA中的β细胞特异性增强子元件。与许多其他病毒和细胞增强剂类似，胰岛素增强剂已被证明具有镶嵌结构，并且对增强剂活性重要的顺式作用元件已被定义。两个短序列对于增强子活性是至关重要的，因为任一序列的突变导致活性降低（约10倍），并且双突变体消除所有增强子活性。这项研究表明，这两个主要的顺式作用元件与β细胞特异性蛋白相互作用。这两个增强子模块具有8个碱基对的同源性，并相互竞争蛋白结合，表明它们与相同的蛋白质相互作用，称为胰岛素增强子结合因子1（IEF 1）。由于这些序列的突变消除了增强子活性和蛋白结合，我们建议IEF 1是控制胰岛素基因增强子选择性活性的关键调节因子。
The selective transcription of the Rat insulin 1 gene is mainly dependent on a beta-cell-specific enhancer element located in the 5' flanking DNA. In analogy to many other viral and cellular enhancers, the insulin enhancer has been shown to be of a mosaic structure and the cis-acting elements of importance for the enhancer activity have been defined. Two short sequences are of crucial importance for the enhancer activity since mutation of either sequence leads to a decrease in activity (by a factor of approximately 10), and the double mutant eliminates all enhancer activity. This study shows that these two major cis-acting elements interact with beta-cell-specific proteins. These two enhancer modules carry an 8-base-pair homology and compete with each other for protein binding, suggesting that they interact with the same protein, designated insulin enhancer binding factor 1 (IEF 1). Since mutation of these sequences eliminates the enhancer activity and protein binding, we propose that IEF 1 is the key regulator controlling the selective activity of the insulin gene enhancer.