Reference : Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highl...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/14997
Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors
English
Delporte, F. M. [> > > >]
Pasque, Vincent mailto [University of Cambridge > Wellcome/Cancer Research UK Gurdon Institute > > >]
Devos, Nathalie mailto [ > > ]
Manfroid, Isabelle mailto [Université de Liège - ULg > > GIGA-Research >]
Voz, Marianne mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Motte, Patrick mailto [Université de Liège - ULg > Département des sciences de la vie > Génomique fonctionnelle et imagerie moléculaire végétale >]
Biemar, Frédéric mailto [Temple University > Department of Biology > > >]
Martial, Joseph mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Peers, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
2008
BMC Developmental Biology
BioMed Central
8
53
Yes (verified by ORBi)
International
1471-213X
[en] Animals ; Animals, Genetically Modified ; Base Sequence ; Conserved Sequence ; DNA-Binding Proteins/chemistry/metabolism ; *Enhancer Elements, Genetic ; Eye Proteins/*genetics ; Gene Expression Regulation, Developmental ; Green Fluorescent Proteins/genetics/metabolism ; Homeodomain Proteins/chemistry/*genetics/metabolism ; Molecular Sequence Data ; Multiprotein Complexes ; Paired Box Transcription Factors/*genetics ; Pancreas/embryology/*metabolism ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Repressor Proteins/*genetics ; Retina/embryology/metabolism ; Sequence Homology, Nucleic Acid ; Telencephalon/embryology/metabolism ; Trans-Activators/chemistry/metabolism ; Transcription Factors/chemistry/metabolism ; Zebrafish/embryology/*genetics/metabolism ; Zebrafish Proteins/chemistry/*genetics/metabolism
[en] BACKGROUND: PAX6 is a transcription factor playing a crucial role in the development of the eye and in the differentiation of the pancreatic endocrine cells as well as of enteroendocrine cells. Studies on the mouse Pax6 gene have shown that sequences upstream from the P0 promoter are required for expression in the lens and the pancreas; but there remain discrepancies regarding the precise location of the pancreatic regulatory elements. RESULTS: Due to genome duplication in the evolution of ray-finned fishes, zebrafish has two pax6 genes, pax6a and pax6b. While both zebrafish pax6 genes are expressed in the developing eye and nervous system, only pax6b is expressed in the endocrine cells of the pancreas. To investigate the cause of this differential expression, we used a combination of in silico, in vivo and in vitro approaches. We show that the pax6b P0 promoter targets expression to endocrine pancreatic cells and also to enteroendocrine cells, retinal neurons and the telencephalon of transgenic zebrafish. Deletion analyses indicate that strong pancreatic expression of the pax6b gene relies on the combined action of two conserved regulatory enhancers, called regions A and C. By means of gel shift assays, we detected binding of the homeoproteins PDX1, PBX and PREP to several cis-elements of these regions. In constrast, regions A and C of the zebrafish pax6a gene are not active in the pancreas, this difference being attributable to sequence divergences within two cis-elements binding the pancreatic homeoprotein PDX1. CONCLUSION: Our data indicate a conserved role of enhancers A and C in the pancreatic expression of pax6b and emphasize the importance of the homeoproteins PBX and PREP cooperating with PDX1, in activating pax6b expression in endocrine pancreatic cells. This study also provides a striking example of how adaptative evolution of gene regulatory sequences upon gene duplication progressively leads to subfunctionalization of the paralogous gene pair.
Giga-Development and Stem Cells
http://hdl.handle.net/2268/14997
10.1186/1471-213X-8-53
2008/05/20

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