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Palmitate increases Nur77 expression by modulating ZBP89 and Sp1 binding to the Nur77 proximal promoter in pancreatic β‐cells
Author(s) -
Mazuy Claire,
Ploton Maheul,
Eeckhoute Jérôme,
Berrabah Wahiba,
Staels Bart,
Lefebvre Philippe,
Helleboid-Chapman Audrey
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.10.024
Subject(s) - nerve growth factor ib , gene knockdown , transfection , pancreatic islets , microbiology and biotechnology , chromatin immunoprecipitation , ornithine decarboxylase antizyme , chemistry , biology , promoter , gene expression , transcription factor , gene , biochemistry , insulin , islet , ornithine decarboxylase , nuclear receptor , endocrinology , enzyme
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.