An engineered zinc finger protein reveals a role for the insulin VNTR in the regulation of the insulin and adjacent IGF2 genes
An engineered zinc finger protein reveals a role for the insulin VNTR in the regulation of the insulin and adjacent IGF2 genes
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DOI：
10.1016/j.febslet.2009.08.041
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发表时间：
2009-10-06
期刊：
影响因子：
3.5
通讯作者：
Docherty, Kevin
中科院分区：
文献类型：
--
作者：
Ferguson, Laura A.;Docherty, Hilary M.;Docherty, Kevin
基于在HEK-293细胞中激活内源性胰岛素基因表达的能力，从文库中分离到一种工程锌指蛋白(EZFP)。利用一组胰岛素启动子结构，eZFP被证明通过位于转录起始点上游365个碱基对的可变数目串联重复(VNTR)区域起作用。EZFP还激活了位于染色体11p15上靠近INS的IGF2基因的表达。这些结果表明，INSVNTR控制胰岛素和IGF2基因的表达，并为以前的研究提供了一个机制解释，这些研究表明INSVNTR型和胎盘中IGF2的水平之间存在关联。(C)2009年欧洲生化学会联合会。爱思唯尔出版，版权所有。
An engineered zinc finger protein (eZFP) was isolated from a library based on its ability to activate expression of the endogenous insulin gene in HEK-293 cells. Using a panel of insulin promoter constructs, the eZFP was shown to act through the variable number of tandem repeat (VNTR) region located 365 base pairs upstream of the transcription start site. The eZFP also activated expression of the IGF2 gene that lies close to INS on chromosome 11p15. These results demonstrate that the INSVNTR controls expression of the insulin and IGF2 genes and provide a mechanistic explanation for previous studies that demonstrated an association between INSVNTR genotypes and placental levels of IGF2. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.