Association of insulin-like growth factor 2 with the insulin-linked polymorphic region in cultured fetal thymus cells.
Association of insulin-like growth factor 2 with the insulin-linked polymorphic region in cultured fetal thymus cells.
复制标题
胰岛素样生长因子 2 与培养的胎儿胸腺细胞中胰岛素相关多态性区域的关联。
DOI：
10.1021/bi900958x
复制
发表时间：
2009
期刊：
影响因子：
2.9
通讯作者：
McGown,LindaB
中科院分区：
文献类型：
--
作者：
Wang,Yuexi;Zhang,Huiping;Ligon,LeeA;McGown,LindaB
胰岛素连锁多态性区（insulin-linked polymorphic region，ILPR）是人胰岛素基因上游启动子区的调控序列，被广泛认为是1型糖尿病易感性的基因座。ILPR序列的多态性可以影响胰岛素和相邻的胰岛素样生长因子2（IGF-2）基因的表达。几种ILPR变体在体外形成G-四链体DNA结构，其表现出与胰岛素和IGF-2的亲和力结合。已经表明ILPR也可以在体内形成G-四链体，这提高了胰岛素和IGF-2可以结合活细胞染色质中ILPR中的这些结构的可能性。这项工作建立了IGF-2存在于从人胎儿胸腺培养的细胞核中，并与这些细胞的染色质中的ILPR相关联。体外实验支持G-四链体DNA参与结合相互作用。
The insulin-linked polymorphic region (ILPR) is a regulatory sequence in the promoter region upstream of the human insulin gene and is widely recognized as a locus of type 1 diabetes susceptibility. Polymorphism of the ILPR sequence can affect expression of both insulin and the adjacent insulin-like growth factor 2 (IGF-2) gene. Several ILPR variants form G-quadruplex DNA structures in vitro that exhibit affinity binding to insulin and IGF-2. It has been suggested that the ILPR may form G-quadruplexes in vivo as well, raising the possibility that insulin and IGF-2 may bind to these structures in the ILPR in chromatin of live cells. This work establishes the presence of IGF-2 in the nucleus of cells cultured from human fetal thymus and its association with the ILPR in the chromatin of these cells. In vitro experiments support the involvement of G-quadruplex DNA in the binding interaction.