title: Characterization of insulin ILPR sequences for their ability to adopt a G-quadruplex structure.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Hanumantharao
authors.initials: H
authors.lastname: Paritala
authors.forename: Steven M
authors.initials: SM
authors.lastname: Firestine
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D054856:G-Quadruplexes / Q000528:radiation effects; D006801:Humans; D007328:Insulin / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation / Q000235:genetics / Q000528:radiation effects; D011110:Polymorphism, Genetic / Q000528:radiation effects; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D013696:Temperature; D014466:Ultraviolet Rays
chemical_list: D007328:Insulin