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

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dc.contributor.authorColes, L.
dc.contributor.authorDiamond, P.
dc.contributor.authorLambrusco, L.
dc.contributor.authorHunter, J.
dc.contributor.authorBurrows, J.
dc.contributor.authorVadas, M.
dc.contributor.authorGoodall, G.
dc.date.issued2002
dc.description.abstractOverexpression 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.
dc.description.statementofresponsibilityColes, Leeanne S ; Diamond, Peter ; Lambrusco, Lidia ; Hunter, Julie ; Burrows, Julie ; Vadas, Mathew A ; Goodall, Gregory J
dc.identifier.citationNucleic Acids Research (NAR), 2002; 30(22):4845-4854
dc.identifier.doi10.1093/nar/gkf615
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.orcidGoodall, G. [0000-0003-1294-0692]
dc.identifier.urihttp://hdl.handle.net/2440/9724
dc.language.isoen
dc.publisherOxford Univ Press
dc.source.urihttps://doi.org/10.1093/nar/gkf615
dc.subject3T3 Cells
dc.subjectCell Nucleus
dc.subjectFibroblasts
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectMice
dc.subjectMacromolecular Substances
dc.subjectIntercellular Signaling Peptides and Proteins
dc.subjectVascular Endothelial Growth Factors
dc.subjectVascular Endothelial Growth Factor A
dc.subjectEndothelial Growth Factors
dc.subjectDNA-Binding Proteins
dc.subjectCCAAT-Enhancer-Binding Proteins
dc.subjectHeat-Shock Proteins
dc.subjectTranscription Factors
dc.subjectRepressor Proteins
dc.subjectDNA, Superhelical
dc.subjectDNA, Single-Stranded
dc.subjectLymphokines
dc.subjectCell Hypoxia
dc.subjectGene Silencing
dc.subjectBinding Sites
dc.subjectBase Sequence
dc.subjectSilencer Elements, Transcriptional
dc.subjectDimerization
dc.subjectMolecular Sequence Data
dc.subjectNFI Transcription Factors
dc.subjectPromoter Regions, Genetic
dc.subjectTranscriptional Activation
dc.titleA 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
dc.typeJournal article
pubs.publication-statusPublished

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