Characterization of Insulin Ilpr Sequences for Their Ability to Adopt a G-Quadruplex Structure

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 29; no. 2; pp. 81 - 90
• Main Authors: Paritala, Hanumantharao, Firestine, Steven M.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 01.02.2010
• Subjects: Base Sequence; Circular Dichroism; class I allele repeats; G-quadruplex; G-Quadruplexes - radiation effects; human insulin gene; Humans; Insulin - genetics; insulin-linked polymorphic repeat region (ILPR); Minisatellite Repeats - genetics; Molecular Sequence Data; Nucleic Acid Denaturation - genetics; Nucleic Acid Denaturation - radiation effects; Polymorphism, Genetic - radiation effects; Repetitive Sequences, Nucleic Acid - genetics; Temperature; type 1 daibetes; Ultraviolet Rays
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257771003597691

A major genetic factor linked to the progression of type 1 diabetes occurs in the insulin-linked polymorphic repeat region (ILPR) located 363 bp upstream of the human insulin gene. Genetic studies have shown that individuals with class I repeats (30-60) are predisposed to the development of type 1 diabetes while individuals with longer repeats are protected. Previous research has suggested that some sequences found within the ILPR can adopt a G-quadruplex structure, and this finding has lead to speculation that G-quadruplexes may control insulin expression in certain circumstances. Unfortunately, relatively little study has been done on whether sequences found in the ILPR can adopt a quadruplex fold. In this study, we have utilized circular dichroism, thermal difference spectroscopy and ultraviolet (UV) melting studies to examine the first seven common repeat sequences (A-G) found in the ILPR. We find that sequences A-E adopt a quadruplex fold while sequences F and G likely do not. Examination of sequence B and a single nucleotide variant, B2, revealed that both folded into a G-quadruplex. This result casts doubt on previous studies suggesting that the formation of a quadruplex was related to the ability of ILPR sequences to regulate transcription.