Transcriptional Regulation of the Mouse Gene Encoding the α-4 Subunit of the GABAA Receptor

• Published in: The Journal of biological chemistry 2004-09, Vol.279 (39), p.40451-40461
• Main Authors: Ma, Limei, Song, Lihua, Radoi, Gina E., Harrison, Neil L.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Brain - metabolism; Cell Nucleus - metabolism; Cells, Cultured; DNA - metabolism; DNA, Complementary - metabolism; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Humans; Luciferases - metabolism; Mice; Mice, Inbred C57BL; Models, Genetic; Molecular Sequence Data; Neurons - metabolism; Plasmids - metabolism; Promoter Regions, Genetic; Protein Binding; Receptors, GABA-A - chemistry; Receptors, GABA-A - genetics; Reverse Transcriptase Polymerase Chain Reaction; Sp3 Transcription Factor; Sp4 Transcription Factor; Synapses - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M406827200

The γ-aminobutyric acid type A receptors (GABAA-Rs) mediate fast inhibitory synaptic transmission in the brain. The α4 subunit of the GABAA-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 α4 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.