BSF1, a Novel Brain-specific DNA-binding Protein Recognizing a Tandemly Repeated Purine DNA Element in the GABA_A Receptor δ Subunit Gene

The rat GABA_A receptor δ subunit gene has been isolated and its promoter mapped to facilitate studies of neuron-specific gene transcription. The gene is transcribed from a single promoter with several clustered transcriptional initiation sites. The major start site maps to a prototype initiator sequence located in the center of a TATA-less CpG-rich island. Analysis of the 5′-flanking region of the GABA_A receptor δ subunit gene revealed a novel tandemly repeated purine sequence element. Furthermore, gel retardation assays identified several tissue-specific and ubiquitous proteins that bind to this sequence. One of these factors, brain-specific factor (BSF) 1, was only observed in extracts from brain and was distinct from BETA and PAL, two DNA-binding proteins with similar purine-rich recognition sequences. The distribution of BSF1 in brain closely matched the expression pattern previously determined for the δ subunit mRNA, and its binding activity appeared simultaneously with GABA_A receptor δ subunit mRNA during differentiation of cerebellar granule cells in vitro. Our data therefore suggest that BSF1 is a novel brain-specific and neuronal cell type-enriched factor possibly involved in differential transcription of the GABA_A receptor δ subunit gene.