The caudal homeobox protein cdx-2/3 activates endogenous proglucagon gene expression in InR1-G9 islet cells.
The proglucagon gene is expressed in a highly cell-specific manner in islet and enteroendocrine cells. DNA sequences within the proximal proglucagon G1 promoter region bind the homeobox protein cdx-2/3, and cdx-2/3 activates the proglucagon promoter in fibroblasts. We show here that cdx-2/3 activates the proglucagon promoter in both islet (InR1-G9) and enteroendocrine (STC-1 and GLUTag) cell lines. Furthermore, transfected cdx-2/3 increased the levels of endogenous proglucagon mRNA transcripts in both transient and stable transfections of InR1-G9 islet cells. The cdx-2/3-dependent induction of endogenous proglucagon mRNA transcripts in stable islet lines was associated with a corresponding increase in the transcriptional activity of proglucagon promoter-luciferase plasmids. An amino-terminally truncated cdx-2/3 derivative containing the homeodomain and carboxy-terminal region of the molecule inhibited both the cdx-2/3 activation of the proglucagon promoter and the induction of endogenous proglucagon mRNA transcripts. These observations demonstrate that cdx-2/3, acting through the proximal G1 element, is a major transcriptional determinant of cell-specific proglucagon gene expression in pancreatic islet cells.
Jin
T
T
Department of Medicine, University of Toronto, Ontario, Canada.
Trinh
D K
DK
Wang
F
F
Drucker
D J
DJ
D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D000071616:CDX2 Transcription Factor; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins; D010957:Plasmids; D016133:Polymerase Chain Reaction; D052336:Proglucagon; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D052336:Proglucagon; D005934:Glucagon; D008156:Luciferases