Regulation of NGFI-A (Egr-1) gene expression by the POU domain transcription factor Brn-3a.

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.