| First Author | Nafez S | Year | 2015 |
| Journal | Mol Cell Neurosci | Volume | 64 |
| Pages | 95-103 | PubMed ID | 25553923 |
| Mgi Jnum | J:231412 | Mgi Id | MGI:5770535 |
| Doi | 10.1016/j.mcn.2014.12.008 | Citation | Nafez S, et al. (2015) Early growth response 2 (Egr-2) expression is triggered by NF-kappaB activation. Mol Cell Neurosci 64:95-103 |
| abstractText | 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-kappaB) are activated in the brain during cancer, brain injury, inflammation, and/or memory. To explore NF-kappaB activity further, we investigated the transcriptomes of hippocampal slices following electrical stimulation of NF-kappaB p50 subunit knockout mice (p50-/-) versus their controls (p50+/+). We found that the early growth response gene Egr-2 was upregulated by NF-kappaB activation, but only in p50+/+ hippocampal slices. We then stimulated HeLa cells and primary cortical neurons with tumor necrosis factor alpha (TNFalpha) to activate NF-kappaB and increase the expression of Egr-2. The Egr-2 promoter sequence was analyzed for NF-kappaB binding sites and chromatin immunoprecipitation (ChIP) assays were performed to confirm promoter occupancy in vivo. We discovered that NF-kappaB specifically binds to an NF-kappaB 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-kappaB activation and Egr-2 expression with Egr-2 expression directly controlled by the transcriptional activity of NF-kappaB. |
