Pax6 and Cdx2/3 form a functional complex on the rat glucagon gene promoter G1-element.
Alpha-cell specific transcription of the glucagon gene is mainly conferred by the glucagon promoter G1-element, while additional elements G2, G3, and G4 have broad islet cell specificity. Transcription of the glucagon gene has been shown to be stimulated by Pax6 through binding to the glucagon gene promoter G3-element. In this report, we show that Pax6 additionally binds the glucagon gene promoter G1-element and forms a transcriptionally active complex with another homeodomain protein, Cdx2/3. Two distinct mutations in the G1-element, that both reduce promoter activity by 85-90%, is shown to eliminate binding of either Pax6 or Cdx2/3. Additionally, Pax6 enhanced Cdx2/3 mediated activation of a glucagon reporter in heterologous cells. We discuss how Pax6 may contribute to cell-type specific transcription in the pancreatic islets by complex formation with different transcription factors.
Andersen
F G
FG
Department of Developmental Biology, Hagedorn Research Institute, Gentofte, Denmark.
Heller
R S
RS
Petersen
H V
HV
Jensen
J
J
Madsen
O D
OD
Serup
P
P
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000071616:CDX2 Transcription Factor; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005136:Eye Proteins; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005934:Glucagon / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D051381:Rats; D012097:Repressor Proteins; D015534:Trans-Activators
D000071616:CDX2 Transcription Factor; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D015534:Trans-Activators; D005934:Glucagon