Palmitate increases Nur77 expression by modulating ZBP89 and Sp1 binding to the Nur77 proximal promoter in pancreatic β-cells

Claire Mazuy; Maheul Ploton; Jérôme Eeckhoute; Wahiba Berrabah; Bart Staels; Philippe Lefebvre; Audrey Helleboid-Chapman

doi:10.1016/j.febslet.2013.10.024

Palmitate increases Nur77 expression by modulating ZBP89 and Sp1 binding to the Nur77 proximal promoter in pancreatic β-cells

FEBS Lett. 2013 Oct 25:S0014-5793(13)00781-3. doi: 10.1016/j.febslet.2013.10.024. Online ahead of print.

Authors

Claire Mazuy¹, Maheul Ploton¹, Jérôme Eeckhoute¹, Wahiba Berrabah¹, Bart Staels¹, Philippe Lefebvre¹, Audrey Helleboid-Chapman¹

Affiliation

¹ 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.

PMID: 24512852
DOI: 10.1016/j.febslet.2013.10.024

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.

Keywords: Nur77; Palmitate; Pancreatic β-cells; Sp1; ZBP89.