title: Identification of GATA-4 as a novel transcriptional regulatory component of regenerating islet-derived family members.
abstract: Intestinal epithelial cells are exposed to luminal bacterial threat and require adequate defense mechanisms to ensure host protection and epithelium regeneration against possible deleterious damage. Differentiated intestinal epithelial cells produce antimicrobial and regenerative components that protect against such challenges. Few intestinal specific transcription factors have been identified to control the switching from repression to activation of this class of gene. Herein, we show that gene transcription of some regenerating islet-derived (REG) family members is dependent on the transcription factor GATA-4. Silencing of GATA-4 expression in cultured intestinal epithelial cells identified Reg3β as a target gene using an unbiased approach of gene expression profiling. Co-transfection and RNA interference assays identified complex GATA-4-interactive transcriptional components required for the activation or repression of Reg3β gene activity. Conditional deletion of Gata4 in the mouse intestinal epithelium supported its regulatory role for Reg1, Reg3α, Reg3β and Reg3γ genes. Reg1 dramatic down-modulation of expression in Gata4 conditional null mice was associated with a significant decrease in intestinal epithelial cell migration. Altogether, these results identify a novel and complex role for GATA-4 in the regulation of REG family members gene expression.
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Lepage
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: Joannie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Brouillard
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Jones
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: Carine R
authors.initials: CR
authors.lastname: Lussier
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rémillard
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: Étienne
authors.initials: É
authors.lastname: Lemieux
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors.forename: Claude
authors.initials: C
authors.lastname: Asselin
authors.affiliation: Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada. Electronic address: francois.boudreau@usherbrooke.ca.
authors.forename: François
authors.initials: F
authors.lastname: Boudreau
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology*; D037181:Lectins, C-Type / Q000378:metabolism; D051847:Lithostathine / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D000073718:Pancreatitis-Associated Proteins; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C541055:Cdx2 protein, rat; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; C084365:Gata4 protein, rat; D018398:Homeodomain Proteins; D037181:Lectins, C-Type; D051847:Lithostathine; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D034741:RNA, Small Interfering; C497615:Reg1 protein, mouse; C490253:Reg3b protein, mouse; C490255:Reg3g protein, mouse; D014157:Transcription Factors
keywords: Cdx-2; FOG; Gata-4; Intestinal epithelial cells; Regenerating islet-derived