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Early growth response 1 (Egr‐1) directly regulates GABA A receptor α2, α4, and θ subunits in the hippocampus
Author(s) -
Mo Jiwon,
Kim ChongHyun,
Lee Dongmin,
Sun Woong,
Lee Hyun Woo,
Kim Hyun
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13077
Subject(s) - glutamatergic , biology , gabaa receptor , homeostatic plasticity , microbiology and biotechnology , synaptic plasticity , chromatin immunoprecipitation , neuroscience , gene expression , receptor , glutamate receptor , promoter , gene , genetics , metaplasticity
The homeostatic regulation of neuronal activity in glutamatergic and GABA ergic 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 A receptor subunit, GABRA 2 (α2), GABRA 4 (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 GABRA 2 , GABRA 4 , 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 A receptor composition in homeostatic plasticity, in a glutamatergic activity‐dependent manner.The early growth response 1 (Egr‐1) is an inducible transcription factor to mediate rapid gene expression by neuronal activity. However, its underlying molecular target genes and mechanisms are not fully understood. We suggest that GABA A receptor subunits, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes are transcriptional targets of Egr‐1. Neuronal activity‐dependent up‐regulation of Egr‐1 might lead to altered subtypes of GABA A receptors for the maintenance of homeostatic excitatory and inhibitory balance for the regulation of synaptic strength.