Early growth response 1 (Egr-1) directly regulates GABA<inf>A</inf> 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

12 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 GABA<inf>A</inf> 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 GABA<inf>A</inf> 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

Fingerprint

GABA-A Receptors
Hippocampus
Growth
Plasticity
Early Growth Response Protein 1
Genes
Messenger RNA
Neuronal Plasticity
Chromatin Immunoprecipitation
Neuroblastoma
Knockout Mice
Synapses
Neurons
Chromatin
Transfection
Real-Time Polymerase Chain Reaction
Brain
Up-Regulation
Networks (circuits)
Chemical analysis

Keywords

  • Chromatin immunoprecipitation
  • Egr-1
  • GABA<inf>A</inf> receptor
  • GABRA2
  • GABRA4
  • GABRQ

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Early growth response 1 (Egr-1) directly regulates GABA<inf>A</inf> receptor α2, α4, and θ subunits in the hippocampus. / Mo, Jiwon; Kim, Chong Hyun; Lee, Dongmin; Sun, Woong; Lee, Hyun Woo; Kim, Hyun.

In: Journal of Neurochemistry, Vol. 133, No. 4, 18.03.2015, p. 489-500.

Research output: Contribution to journalArticle

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