title: Identification of transcription factors involved in the transcriptional regulation of the CXCL12 gene in rat pancreatic insulinoma Rin-5F cell line.
abstract: Diabetes is characterized by a deficit in the number of functional pancreatic β-cells. Understanding the mechanisms that stimulate neogenesis of β-cells should contribute to improved maintenance of β-cell mass. Chemokine CXCL12 has recently become established as a novel β-cell growth factor, however the mechanisms controlling its expression require clarification. We investigated the proteins involved in the transcriptional regulation of the rat β-cell CXCL12 gene (Cxcl12). Using the electrophoretic mobility shift assay and chromatin immunoprecipitation, we established the in vitro and in vivo binding of C/EBPβ, C/EBPα, STAT3, p53, FOXO3a, and HMG I/Y to the Cxcl12 promoter. Co-immunoprecipitation experiments revealed protein-protein interactions between YY1 and PARP-1, FOXO3a and PARP-1, Sp1 and PARP-1, p53 and PARP-1, C/EBPβ and PARP-1, YY1 and p53, YY1 and FOXO3a, p53 and FOXO3a, Sp1 and FOXO3a, C/EBPβ and FOXO3a, C/EBPα and FOXO3a, Sp1 and STAT3. Our data lay the foundation for research into the interplay of signaling pathways that determine the β-cell Cxcl12 expression profile.
authors.affiliation: a Department of Molecular Biology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 10060 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Marković
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Uskoković
authors.forename: Nevena
authors.initials: N
authors.lastname: Grdović
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dinić
authors.forename: Mirjana
authors.initials: M
authors.lastname: Mihailović
authors.forename: Jelena Arambašić
authors.initials: JA
authors.lastname: Jovanović
authors.forename: Goran
authors.initials: G
authors.lastname: Poznanović
authors.forename: Melita
authors.initials: M
authors.lastname: Vidaković
mesh_terms: D000818:Animals; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C575935:CXCL12 protein, rat; C545014:Cebpb protein, rat; D054377:Chemokine CXCL12; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D011065:Poly(ADP-ribose) Polymerases
keywords: CXCL12; CXCL12 gene promoter; interaction facteur de transcription-promoteur; interaction protéine–protéine; promoteur du gène de CXCL12; protein–protein interaction; régulation transcriptionnelle; transcription factor-promoter interaction; transcriptional regulation