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The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription

Nature Genetics volume 9, pages 293–298 (1995)Cite this article

Abstract

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 β–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.

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Author notes

  1. Giulia Catignani Kennedy

    Present address: Millennium Pharmaceuticals, Inc., 640 Memorial Drive, Cambridge, Massachusetts, 02139-4815

Authors and Affiliations

  1. Hormone Research Institute and the Department of Biochemistry & Biophysics, University of California, San Francisco, California, 94143-0534, USA

    Giulia Catignani Kennedy & William J. Rutter

  2. Department of Medicine, University of California, San Francisco, California, 94143-0534, USA

    Michael S. German

Authors
  1. Giulia Catignani Kennedy
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  2. Michael S. German
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  3. William J. Rutter
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Kennedy, G., German, M. & Rutter, W. The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription. Nat Genet 9, 293–298 (1995). https://doi.org/10.1038/ng0395-293

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