This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by D'Arcangelo, G. Articles by Salton, S. R. Search for Related Content PubMed PubMed Citation Articles by D'Arcangelo, G. Articles by Salton, S. R.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 09 1996, 4621-4631, Vol 16, No. 9
Copyright © 1996, American Society for Microbiology

Activation of codependent transcription factors is required for transcriptional induction of the vgf gene by nerve growth factor and Ras

G D'Arcangelo, R Habas, S Wang, S Halegoua and SR Salton
Department of Neurobiology and Behavior and Institute for Cell and Developmental Biology, State University of New York at Stony Brook, 11794-5230, USA.

Nerve growth factor (NGF) treatment of PC12 cells leads to the elaboration of a neuronal phenotype, including the induction of neuronally expressed genes such as vgf. To study vgf transcription, we have created chimeric vgf/beta-globin genes in which vgf promoter sequences drive the expression of the beta-globin reporter gene or of a chimeric beta-globin gene fused to 3' untranslated vgf gene sequences. We have found that the level of inducibility of the latter construct by NGF resembles that of the endogenous vgf gene. Using transient transfection of the chimeric reporter genes into PC12 cells, into PC12 subclones expressing activated or dominantly interfering mutant Ras proteins, and into PC12 variants expressing specific NGF receptor/Trk mutants, we show that transcriptional regulation of the vgf promoter by NGF is mediated through a Ras-dependent signaling pathway. By mutational analysis of the vgf promoter, we have identified three promoter elements involved in mediating transcriptional induction by NGF and Ras. In addition to the cyclic AMP-responsive element (CRE), which binds to ATF-1, ATF-2, and CRE-binding protein in PC12 nuclear extracts, a novel CCAAT element and its binding proteins were identified, which, like the CRE, is necessary but not sufficient for the Ras-dependent induction of the vgf gene by NGF. We also identify a G(S)G element unusually located between the TATA box and transcriptional start site, which binds the NGF- and Ras-induced transcription factor, NGFI-A, and amplifies the transcriptional response. Integrating data from studies of vgf promoter regulation and NGF signal transduction, we present a model for vgf gene induction in which transcriptional activation is achieved through the persistent, direct activation of multiple interacting transcription factors binding to CRE and CCAAT elements, coordinated with the delayed transcription factor action at a G(S)G element resulting from the induced expression of NGFI-A.

This article has been cited by other articles:

• Birk, D. M., Barbato, J., Mureebe, L., Chaer, R. A. (2009). Basic Science Review: Current Insights on the Biology and Clinical Aspects of VEGF Regulation. VASC ENDOVASCULAR SURG 42: 517-530 [Abstract]  
• Nashat, A. H., Langer, R. (2003). Temporal Characteristics of Activation, Deactivation, and Restimulation of Signal Transduction following Depolarization in the Pheochromocytoma Cell Line PC12. Mol. Cell. Biol. 23: 4788-4795 [Abstract] [Full Text]  
• Hahm, S., Fekete, C., Mizuno, T. M., Windsor, J., Yan, H., Boozer, C. N., Lee, C., Elmquist, J. K., Lechan, R. M., Mobbs, C. V., Salton, S. R. J. (2002). VGF is Required for Obesity Induced by Diet, Gold Thioglucose Treatment, and Agouti and is Differentially Regulated in Pro-Opiomelanocortin- and Neuropeptide Y-Containing Arcuate Neurons in Response to Fasting. J. Neurosci. 22: 6929-6938 [Abstract] [Full Text]  
• Choi, D.-Y., Toledo-Aral, J. J., Segal, R., Halegoua, S. (2001). Sustained Signaling by Phospholipase C-{gamma} Mediates Nerve Growth Factor-Triggered Gene Expression. Mol. Cell. Biol. 21: 2695-2705 [Abstract] [Full Text]  
• Boss, V., Roback, J. D., Young, A. N., Roback, L. J., Weisenhorn, D. M. V., Medina-Flores, R., Wainer, B. H. (2001). Nerve Growth Factor, But Not Epidermal Growth Factor, Increases Fra-2 Expression and Alters Fra-2/JunD Binding to AP-1 and CREB Binding Elements in Pheochromocytoma (PC12) Cells. J. Neurosci. 21: 18-26 [Abstract] [Full Text]