Article (Scientific journals)
Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors
Delporte, F. M.; Pasque, Vincent; Devos, Nathalie et al.
2008In BMC Developmental Biology, 8, p. 53
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Keywords :
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
Abstract :
[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.
Research center :
Giga-Development and Stem Cells - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Delporte, F. M.
Pasque, Vincent;  University of Cambridge > Wellcome/Cancer Research UK Gurdon Institute
Devos, Nathalie
Manfroid, Isabelle ;  Université de Liège - ULiège > GIGA-Research
Voz, Marianne  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Motte, Patrick ;  Université de Liège - ULiège > Département des sciences de la vie > Génomique fonctionnelle et imagerie moléculaire végétale
Biemar, Frédéric;  Temple University > Department of Biology
Martial, Joseph ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Peers, Bernard ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Language :
English
Title :
Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors
Publication date :
2008
Journal title :
BMC Developmental Biology
eISSN :
1471-213X
Publisher :
BioMed Central
Volume :
8
Pages :
53
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 22 June 2009

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