Association of Insulin-like Growth Factor 2 with the Insulin-Linked Polymorphic Region in Cultured Fetal Thymus Cells

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.