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

C Mazuy, M Ploton, J Eeckhoute, W Berrabah, B Staels… - FEBS letters, 2013 - Elsevier
C Mazuy, M Ploton, J Eeckhoute, W Berrabah, B Staels, P Lefebvre, A Helleboid-Chapman
FEBS letters, 2013Elsevier
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 …
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.
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