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: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, France; Inserm UMR 1011, F-59000 Lille, France; IPL, F-59000 Lille, France.
authors: Claire
authors: C
authors: Mazuy
authors: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, France; Inserm UMR 1011, F-59000 Lille, France; IPL, F-59000 Lille, France.
authors: Maheul
authors: M
authors: Ploton
authors: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, France; Inserm UMR 1011, F-59000 Lille, France; IPL, F-59000 Lille, France.
authors: Jérôme
authors: J
authors: Eeckhoute
authors: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, France; Inserm UMR 1011, F-59000 Lille, France; IPL, F-59000 Lille, France.
authors: Wahiba
authors: W
authors: Berrabah
authors: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, France; Inserm UMR 1011, F-59000 Lille, France; IPL, F-59000 Lille, France.
authors: Bart
authors: B
authors: Staels
authors: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, France; Inserm UMR 1011, F-59000 Lille, France; IPL, F-59000 Lille, France.
authors: Philippe
authors: P
authors: Lefebvre
authors: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; UNIV LILLE 2, F-59000 Lille, France; Inserm UMR 1011, F-59000 Lille, France; IPL, F-59000 Lille, France.
authors: Audrey
authors: A
authors: Helleboid-Chapman
keywords: Nur77; Palmitate; Pancreatic β-cells; Sp1; ZBP89