Journal
BIOCHEMISTRY
Volume 48, Issue 34, Pages 8189-8194Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi900958x
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Funding
- National Institutes of Health [IR21DK70762]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK070762] Funding Source: NIH RePORTER
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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 I 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.
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