The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription.
Genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) is inherited as a polygenic trait. One of the loci implicated in IDDM is a polymorphic minisatellite 5' of the human insulin (INS) gene on chromosome 11. This insulin-linked polymorphic region (ILPR) is composed of tandemly repeated sequences, which fall into three size classes: IDDM is strongly associated with short ILPR alleles. We now show that the ILPR is capable of transducing a transcriptional signal in pancreatic beta-cells, with a long ILPR possessing greater activity than a short ILPR. The ILPR contains numerous high-affinity binding sites for the transcription factor Pur-1, and transcriptional activation by Pur-1 is modulated by naturally occurring sequences in the ILPR. Our results demonstrate a possible function for this unique minisatellite, which may have implications for type 1 diabetes.
Kennedy
G C
GC
Hormone Research Institute, University of California, San Francisco 94143-0534, USA.
German
M S
MS
Rutter
W J
WJ
D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D004276:DNA, Satellite / Q000235:genetics; D004268:DNA-Binding Proteins; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007515:Islets of Langerhans / Q000378:metabolism; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D007328:Insulin; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein