Pax4 regulatory elements mediate beta cell specific expression in the pancreas.
Pax4 is a member of the Pax (Pax, paired box) family of transcription factors with restricted expression and essential functions in the developing pancreas. Pax4 deficient mice do not develop pancreatic beta and delta cells and thus die after birth due to diabetes. In this study using transgenic mouse technology we report the identification and characterization of a 0.9 kb DNA fragment in the 5'-region of the gene, which by itself is able to direct Pax4 expression in the endocrine pancreas, recapitulating the beta-cell-specific in vivo expression pattern of Pax4. The 0.9 kb DNA fragment contains an area spanning 407 base pairs that is highly conserved between human and mouse showing 88% identity. This promoter region contains sequence motifs that have been shown to be involved in beta-cell-specific expression of insulin, Pdx1 and islet amyloid polypeptide (IAPP). In addition, we determined a previously undescribed 5'intron.
Brink
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C
Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Chowdhury
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K
Gruss
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P
D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000196:embryology / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D051761:Paired Box Transcription Factors; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism*; D014158:Transcription, Genetic
D000682:Amyloid; D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; C496503:Foxa2 protein, mouse; D018398:Homeodomain Proteins; D058228:Islet Amyloid Polypeptide; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; C084010:pancreatic and duodenal homeobox 1 protein; D051542:Hepatocyte Nuclear Factor 3-beta