title: CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors.
abstract: Expression of the nuclear orphan receptor gene Nur77 in neuronal cells is induced by activity-dependent increases in intracellular Ca2+ ions. Ca2+ responsiveness of the Nur77 gene has been attributed to two distinct DNA regulatory regions that recruit the transcription factors cAMP response element binding protein (CREB) and myocyte enhancer factor-2 (MEF2). Here we used dominant interfering and constitutively active mutants of CREB and MEF2 proteins to assess their relative contribution to depolarization-induced Nur77 expression in undifferentiated PC12 cells and hippocampal neurons. We show that while CREB is necessary for Ca2+-activated Nur77 expression MEF2 functions to modulate CREB-dependent Nur77 expression by acting as a repressor in quiescent cells.
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, UK.
authors.forename: Brian Yee Hong
authors.initials: BY
authors.lastname: Lam
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhang
authors.forename: David Chi-Heng
authors.initials: DC
authors.lastname: Ng
authors.forename: Mahiben
authors.initials: M
authors.lastname: Maruthappu
authors.forename: Hywel Llewelyn
authors.initials: HL
authors.lastname: Roderick
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Chawla
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D009154:Mutation / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D050778:NFATC Transcription Factors; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D016572:Cyclosporine; D050882:CREB-Binding Protein; D002118:Calcium