Early Growth Response 2 (Egr2) Induction by Neuronal Activity-dependent Nuclear Factor Kappa B (NF-κB) Activation

Abstract

Nuclear factor kappa B (NF-κB) mediated signalling is complex and plays a critical role in many biological processes. Investigators have reported that NF-κB is activated during the induction of long term potentiation (LTP), a proposed mechanism for memory encoding, and may be a requirement for synaptic plasticity and memory. In this study, mRNA extracted from hippocampal slices of NF-kB p50 knockout mice and its littermate before and after induction of LTP was analyzed using DNA microarray analysis (Affy-metrix GeneChip® Mouse Genome 430 2.0) to explore candidate target genes of NF-kB in LTP. The early growth response 2 (Egr-2) was identified as one putative NF-kB target gene. Egr-2 mRNA and protein analysis of primary cortical neurons and HeLa cells chemically stimulated with Tumor Necrosis Factor α (TNFα) to activate the NF-kB sig-nalling pathway confirmed the microarray results. In addition, examination of the Egr-2 promoter sequence for NF-kB binding sites using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSA) confirmed promoter occupancy and specificity of binding in vivo, respectively. These data suggest that Egr-2 expression level is controlled by direct transcriptional activity of the NF-kB transcription factor.