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J. Biol. Chem., Vol. 279, Issue 39, 40451-40461, September 24, 2004

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Transcriptional Regulation of the Mouse Gene Encoding the -4 Subunit of the GABA_A Receptor^*

Limei Ma, Lihua Song, Gina E. Radoi, and Neil L. Harrison

From the Departments of Anesthesiology and Pharmacology, Weill Medical College, Cornell University, New York, New York 10021

The -aminobutyric acid type A receptors (GABA_A-Rs) mediate fast inhibitory synaptic transmission in the brain. The 4 subunit of the GABA_A-R confers distinct pharmacological properties on the receptor and its expression pattern exhibits plasticity in response to physiological and pharmacological stimuli, including withdrawal from progesterone and alcohol. We have analyzed the promoter region of the mouse GABRA4 gene that encodes the 4 subunit and found that the promoter has multiple transcriptional initiation sites and lacks a TATA box. The minimal promoter for GABRA4 spans the region between –444 to –19 bp relative to the coding ATG and shows high activity in cultured mouse cortical neurons. Both Sp3 and Sp4 transcription factors can interact with the two Sp1 binding sites within the minimal promoter and are critical for maximal activity of the promoter in neurons.

Received for publication, June 18, 2004

^* This work was supported in part by National Institute on Alcohol Abuse and Alcoholism Grant AA13646 (to N. L. H.) and a Charles Dana Foundation Postdoctoral Fellowship (to L. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by the Dept. of Anesthesiology at the Weill Cornell Medical College to the CV Starr laboratory. To whom correspondence should be addressed: 525 East 68th St., A-1040, New York, NY 10021. Tel.: 212-746-1150; Fax: 212-746-4879; E-mail: neh2001{at}med.cornell.edu.

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