title: Regulation of NGFI-A (Egr-1) gene expression by the POU domain transcription factor Brn-3a.
abstract: NGFI-A is an immediate early gene (IEG) that is transcriptionally induced by nerve growth factor (NGF) in PC12 cells and has been implicated in a number of cellular responses. Studies have shown that elements within the first 106 base pairs of the NGFI-A promoter contribute to its induction by NGF in PC12 cells. One element, within the serum response element (SRE) bridge region, bears strong homology to a motif previously identified in promoters regulated by the Brn-3a POU domain transcription factor. We report here that Brn-3a activates the NGFI-A promoter in neurons (both primary and cell lines). Analysis revealed that this response requires sequences between positions -49 and -106. Whilst DNA-protein interaction studies failed to identify a site bound directly by Brn-3a, the data presented here suggest that Brn-3a may cooperate in the regulation of NGFI-A gene expression in neurons, possibly during the developmental switch between neurotrophin dependency that occurs during neurogenesis.
authors.affiliation: Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Smith
authors.forename: E A
authors.initials: EA
authors.lastname: Ensor
authors.forename: L
authors.initials: L
authors.lastname: Stohl
authors.forename: J A
authors.initials: JA
authors.lastname: Wagner
authors.forename: D S
authors.initials: DS
authors.lastname: Latchman
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects; D006822:Hybrid Cells; D017874:Immediate-Early Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020218:Response Elements / Q000235:genetics; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014709:Vero Cells
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; C494189:Pou4f1 protein, mouse; D011993:Recombinant Fusion Proteins; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D003907:Dexamethasone