Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus
- Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus
- 모지원; 김종현; 이동민; 선웅; 이현우; 김현
- Egr-1; GABAA; receptor,
- Issue Date
- Journal of neurochemistry
- VOL 133, 489-500
- The homeostatic regulation of neuronal activity in glutamatergic and GABAergic synapses is critical for neural circuit development and synaptic plasticity. The induced expression of the transcription factor early growth response 1 (Egr-1) in neurons is tightly associated with many forms of neuronal activity, but the underlying target genes in the brain remained to be elucidated. This study uses a quantitative real-time PCRapproach, in combination with in vivo chromatin immunoprecipitation, and reveals that GABAA receptor subunit, GABRA2 (a2), GABRA4 (a4), and GABRQ (h) genes, are transcriptional targets of Egr-1. Transfection of a construct that overexpresses Egr-1 in neuroblastoma (Neuro2A) cells up-regulates the a2, a4, and h subunits. Given that Egr-1 knockout mice display less GABRA2, GABRA4, and GRBRQ mRNA in the hippocampus, and that Egr-1 directly binds to their promoters and induces mRNA expression, the present findings support a role for Egr-1 as a major regulator for altered GABAA receptor composition in homeostatic plasticity, in a glutamatergic activity-dependent manner
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