Insulin upstream factor 1 and a novel ubiquitous factor bind to the human islet amyloid polypeptide/amylin gene promoter.
The islet amyloid polypeptide (IAPP) gene is expressed primarily in the islet beta-cell and the peptide is co-secreted with insulin. To investigate mechanisms important in its regulation, we have used the electrophoretic mobility-shift assay and methylation interference to determine systematically sites of DNA-protein interactions in the human IAPP promoter. We identified beta-cell-specific DNA-protein complexes at three sites, each of which contained a consensus binding site for insulin upstream factor I (IUF-I). This complex was displaced with an antiserum to IUF-1, confirming that IUF-1 binds to the human IAPP promoter in vitro. We have also identified a DNA-protein complex within the region -220/-250 in both beta- and non-beta-cell lines. This region contains a motif with partial identity with the binding site for the ubiquitous transcription factor upstream stimulatory factor ( USF), which binds to the human insulin promoter. However, purified USF was not able to bind to this putative site in the IAPP promoter and an oligonucleotide containing a functional USF- binding site was unable to displace binding from the IAPP oligonucleotide. Methylation interference revealed that the DNA-protein complex binds to a sequence that overlaps the USE-like sequence, and may therefore be a novel helix-loop-helix protein. These results suggest that, although both IAPP and insulin are beta-cell peptides, IAPP contains regulatory regions both common to and distinct from insulin.[1]References
- Insulin upstream factor 1 and a novel ubiquitous factor bind to the human islet amyloid polypeptide/amylin gene promoter. Bretherton-Watt, D., Gore, N., Boam, D.S. Biochem. J. (1996) [Pubmed]
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