期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2000
卷号:97
期号:23
页码:12508-12512
DOI:10.1073/pnas.97.23.12508
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:One of the loci responsible for genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) is the insulin-linked polymorphic region (ILPR, also known as IDDM2). This polymorphic G-rich minisatellite, located in the promoter region of the human insulin gene, comprises a variable number of tandemly repeating sequences related to ACAGGGGTGTGGGG. An interesting characteristic of the ILPR is its ability to form unusual DNA structures in vitro, presumably through formation of G-quartets. This ability to form G-quartets raises the intriguing possibility that transcriptional activity of the insulin gene may in fact be influenced by the quaternary DNA topology of the ILPR. We now show that single nucleotide differences in the ILPR known to affect insulin transcription are correlated with ability to form unusual DNA structures. Through the design and testing of two high transcriptional activity ILPR repeats, we demonstrate that both inter- and intramolecular G-quartet formation in the ILPR can influence transcriptional activity of the human insulin gene, and thus, may contribute to that portion of diabetes susceptibility attributed to the IDDM2 locus.
关键词:G-quartets ; tetrastrand DNA ; variable number of tandem repeats ; insulin gene-linked polymorphic region