Sequential expression of Egr-1 and Egr-3 in hippocampal granule cells following electroconvulsive stimulation.

Previous studies examining the regulation of immediate early gene mRNAs by neuronal stimulation have revealed that two members of the Egr family of transcription factors, Egr-1 and Egr-3, display parallel response patterns. As these transcription factors compete for the same consensus sequence, we investigated how their expression and DNA binding activities are coordinated. Following electroconvulsive stimulation, which induces rapid increases in both Egr-1 and Egr-3 mRNA levels in dentate granule cells, we found that these proteins are induced sequentially. Egr-1 protein levels peak at 0.5-1 h and decay to basal levels by 4 h. In contrast, Egr-3 protein levels respond more slowly; little change is apparent at 1 h, and peak levels are not reached until 4 h following stimulation. Gel shift assays demonstrated that Egr-1 and Egr-3 DNA binding activities follow the same pattern. These findings indicate that Egr-1 and Egr-3 act in concert to mediate early and late phases, respectively, of the transcriptional response regulated by their cognate response element.