| First Author | Melloul D | Year | 2002 |
| Journal | Diabetes | Volume | 51 Suppl 3 |
| Pages | S320-5 | PubMed ID | 12475770 |
| Mgi Jnum | J:80445 | Mgi Id | MGI:2445880 |
| Doi | 10.2337/diabetes.51.2007.s320 | Citation | Melloul D, et al. (2002) Regulation of pdx-1 gene expression. Diabetes 51 Suppl 3:S320-5 |
| abstractText | The homeodomain-containing transcription factor pancreatic duodenal homeobox 1 (PDX-1) plays a key role in pancreas development and in beta-cell function. Upstream sequences of the gene up to about -6 kb show islet-specific activity in transgenic mice. Attempts to identify functional regulatory elements involved in the controlled expression of the pdx-1 gene led to the identification of distinct distal beta-cell-specific enhancers in human and rat genes. Three additional sequences, conserved between the mouse and the human 5'-flanking regions, two of which are also found in the chicken gene, conferred beta-cell-specific expression on a reporter gene, albeit to different extents. A number of transcription factors binding to and modulating the transcriptional activity of the regulatory elements were identified, such as hepatocyte nuclear factor (HNF)-3beta, HNF-1alpha, SP1/3, and, interestingly, PDX-1 itself. A fourth conserved region was localized to the proximal promoter around an E-box motif and was found to bind members of the upstream stimulatory factor (USF) family of transcription factors. We postulate that disruption of pdx-1 cis-acting regulatory sequences and/or mutations or functional impairment of transcription factors controlling the expression of the gene can lead to diabetes. |
