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https://hdl.handle.net/2440/9724
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Type: | Journal article |
Title: | A novel mechanism of repression of the vascular endothelial growth factor promoter, by single strand DNA binding cold shock domain (Y-box) proteins in normoxic fibroblasts |
Author: | Coles, L. Diamond, P. Lambrusco, L. Hunter, J. Burrows, J. Vadas, M. Goodall, G. |
Citation: | Nucleic Acids Research, 2002; 30(22):4845-4854 |
Publisher: | Oxford Univ Press |
Issue Date: | 2002 |
ISSN: | 0305-1048 1362-4962 |
Statement of Responsibility: | Coles, Leeanne S ; Diamond, Peter ; Lambrusco, Lidia ; Hunter, Julie ; Burrows, Julie ; Vadas, Mathew A ; Goodall, Gregory J |
Abstract: | Overexpression of vascular endothelial growth factor (VEGF) is implicated in a number of diseases. It is therefore critical that mechanisms exist to strictly regulate VEGF expression. A hypoxia-responsive (HR) region of the VEGF promoter which binds the HIF-1 transcription factor is a target for many signals that up-regulate VEGF transcription. Repressors targeting the HIF-1 transcription factor have been identified but no repressors directly binding the HR promoter region had been reported. We now report a novel mechanism of repression of the VEGF HR region involving DNA binding. We find that single strand DNA-specific cold shock domain (CSD or Y-box) proteins repress the HR region via a binding site downstream of the HIF-1 site. The repressor site is functional in unstimulated, normoxic fibroblasts and represents a novel means to prevent expression of VEGF in the absence of appropriate stimuli. We characterized complexes forming on the VEGF repressor site and identified a previously unreported nuclear CSD protein complex containing dbpA. Nuclear dbpA appears to bind as a dimer and we determined a means by which nuclear CSD proteins may enter double strand DNA to bind to their single strand sites to bring about repression of the VEGF HR region. |
Keywords: | 3T3 Cells Cell Nucleus Fibroblasts Animals Mice, Inbred BALB C Mice Macromolecular Substances Intercellular Signaling Peptides and Proteins Vascular Endothelial Growth Factors Vascular Endothelial Growth Factor A Endothelial Growth Factors DNA-Binding Proteins CCAAT-Enhancer-Binding Proteins Heat-Shock Proteins Transcription Factors Repressor Proteins DNA, Superhelical DNA, Single-Stranded Lymphokines Cell Hypoxia Gene Silencing Binding Sites Base Sequence Silencer Elements, Transcriptional Dimerization Molecular Sequence Data NFI Transcription Factors Promoter Regions, Genetic Transcriptional Activation |
DOI: | 10.1093/nar/gkf615 |
Published version: | http://dx.doi.org/10.1093/nar/gkf615 |
Appears in Collections: | Aurora harvest Medicine publications |
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