title: Palmitate increases Nur77 expression by modulating ZBP89 and Sp1 binding to the Nur77 proximal promoter in pancreatic β-cells.
abstract: Nur77 is a stress sensor in pancreatic β-cells, which negatively regulates glucose-stimulated insulin secretion. We recently showed that a lipotoxic shock caused by exposure of β-cells to the saturated fatty acid palmitate strongly increases Nur77 expression. Here, using dual luciferase reporter assays and Nur77 promoter deletion constructs, we identified a regulatory cassette between -1534 and -1512 bp upstream from the translational start site mediating Nur77 promoter activation in response to palmitate exposure. Chromatin immunoprecipitation, transient transfection and siRNA-mediated knockdown assays revealed that palmitate induced Nur77 promoter activation involves Sp1 recruitment and ZBP89 release from the gene promoter.
authors.forename: Claire
authors.initials: C
authors.lastname: Mazuy
authors.forename: Maheul
authors.initials: M
authors.lastname: Ploton
authors.forename: Jérôme
authors.initials: J
authors.lastname: Eeckhoute
authors.forename: Wahiba
authors.initials: W
authors.lastname: Berrabah
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Audrey
authors.initials: A
authors.lastname: Helleboid-Chapman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics* / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C491741:Zfp148 protein, mouse; D019308:Palmitic Acid