THE INSULIN ENHANCER-BINDING SITE-2 (IEB2 FAR) BOX OF THE INSULIN GENE REGULATORY REGION BINDS AT LEAST 3 FACTORS THAT CAN BE DISTINGUISHED BY THEIR DNA-BINDING CHARACTERISTICS

Located at approximately 230 bp upstream from the transcription start site, the insulin enhancer binding site 2 (IEB2) or FAR region of the insulin gene is one of several important sequences involved in regulating transcription of the gene. The present study was undertaken to characterize the transcription factors binding at the IEB2/FAR region of the rat insulin II gene and to compare these with factors known to bind to the equivalent sequence in the rat I and human insulin genes. An endocrine-enriched factor, EFD3, was identified, which bound to the sequence CAGGAG. A second factor (D4) was identified as the widely expressed factor USF (upstream stimulating factor), while a third factor (D5) remained largely uncharacterized. The binding affinities of these three factors differed in the three genes, suggesting that the role of the IEB2/FAR sequence may vary subtly between the rat insulin II, rat insulin I and human insulin genes.