Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus

Jiwon Mo, Chong Hyun Kim, Dongmin Lee, Woong Sun, Hyun Woo Lee, Hyun Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 PCR approach, in combination with in vivo chromatin immunoprecipitation, and reveals that GABAA receptor subunit, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes, are transcriptional targets of Egr-1. Transfection of a construct that over-expresses Egr-1 in neuroblastoma (Neuro2A) cells up-regulates the α2, α4, and θ 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.

Original languageEnglish
Pages (from-to)489-500
Number of pages12
JournalJournal of Neurochemistry
Volume133
Issue number4
DOIs
Publication statusPublished - 2015 Mar 18

Keywords

  • Chromatin immunoprecipitation
  • Egr-1
  • GABA receptor
  • GABRA2
  • GABRA4
  • GABRQ

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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