title: Early growth response 2 (Egr-2) expression is triggered by NF-κB activation.
abstract: Transcription factors are known to play multiple roles in cellular function. Investigators report that factors such as early growth response (Egr) protein and nuclear factor kappa B (NF-κB) are activated in the brain during cancer, brain injury, inflammation, and/or memory. To explore NF-κB activity further, we investigated the transcriptomes of hippocampal slices following electrical stimulation of NF-κB p50 subunit knockout mice (p50-/-) versus their controls (p50+/+). We found that the early growth response gene Egr-2 was upregulated by NF-κB activation, but only in p50+/+ hippocampal slices. We then stimulated HeLa cells and primary cortical neurons with tumor necrosis factor alpha (TNFα) to activate NF-κB and increase the expression of Egr-2. The Egr-2 promoter sequence was analyzed for NF-κB binding sites and chromatin immunoprecipitation (ChIP) assays were performed to confirm promoter occupancy in vivo. We discovered that NF-κB specifically binds to an NF-κB consensus binding site within the proximal promoter region of Egr-2. Luciferase assay demonstrated that p50 was able to transactivate the Egr-2 promoter in vitro. Small interfering RNA (siRNA)-mediated p50 knockdown corroborated other Egr-2 expression studies. We show for the first time a novel link between NF-κB activation and Egr-2 expression with Egr-2 expression directly controlled by the transcriptional activity of NF-κB.
authors.affiliation: St. Boniface Hospital Research; University of Manitoba, Dept. of Pharmacology & Therapeutics, Winnipeg MB, Canada.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Nafez
authors.affiliation: St. Boniface Hospital Research; University of Manitoba, Dept. of Pharmacology & Therapeutics, Winnipeg MB, Canada.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oikawa
authors.affiliation: St. Boniface Hospital Research, Winnipeg MB, Canada.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Odero
authors.affiliation: St. Boniface Hospital Research, Winnipeg MB, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Sproule
authors.affiliation: St. Boniface Hospital Research, Winnipeg MB, Canada.
authors.forename: Ning
authors.initials: N
authors.lastname: Ge
authors.affiliation: St. Boniface Hospital Research; University of Manitoba, Dept. of Pharmacology & Therapeutics, Winnipeg MB, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Schapansky
authors.affiliation: St. Boniface Hospital Research, Winnipeg MB, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Abrenica
authors.affiliation: St. Boniface Hospital Research, Winnipeg MB, Canada.
authors.forename: Avril
authors.initials: A
authors.lastname: Hatherell
authors.affiliation: St. Boniface Hospital Research; University of Manitoba - Graduate Program in Biomedical Engineering, Winnipeg MB, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Cadonic
authors.affiliation: Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg MB, Canada.
authors.forename: Shunzhen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Dept. of Medical Genetics, University of Alberta, Edmonton AB, Canada.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Song
authors.affiliation: University of Manitoba, Dept. of Pharmacology & Therapeutics, Winnipeg MB, Canada.
authors.forename: Tiina
authors.initials: T
authors.lastname: Kauppinen
authors.affiliation: St. Boniface Hospital Research; University of Manitoba, Dept. of Pharmacology & Therapeutics, Winnipeg MB, Canada.
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Glazner
authors.affiliation: Dept. Pharmaceutical Sciences, University of Piemonte Orientale, Novara Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Grilli
authors.affiliation: St. Boniface Hospital Research; University of Manitoba, Dept. of Physiology, Winnipeg MB, Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czubryt
authors.affiliation: Depts. of Pediatrics, Medical Genetics and Oncology, University of Alberta, Edmonton AB, Canada.
authors.forename: David D
authors.initials: DD
authors.lastname: Eisenstat
authors.affiliation: St. Boniface Hospital Research; University of Manitoba - Graduate Program in Biomedical Engineering; University of Manitoba, Dept. of Pharmacology & Therapeutics, Winnipeg MB, Canada. Electronic address: balbensi@sbrc.ca.
authors.forename: Benedict C
authors.initials: BC
authors.lastname: Albensi
mesh_terms: D000818:Animals; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation
chemical_list: D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D052002:NF-kappa B p50 Subunit
keywords: Egr; Gene expression; Memory; NF-κB; Signal transduction; Transcription factor