Abstract
BackgroundSubtypes of the GABAA receptor subunit exhibit diverse temporal and spatial expression patterns. In silico comparative analysis was used to predict transcriptional regulatory features in individual mammalian GABAA receptor subunit genes, and to identify potential transcriptional regulatory components involved in the coordinate regulation of the GABAA receptor gene clusters.ResultsPreviously unreported putative promoters were identified for the β2, γ1, γ3, ε, θ and π subunit genes. Putative core elements and proximal transcriptional factors were identified within these predicted promoters, and within the experimentally determined promoters of other subunit genes. Conserved intergenic regions of sequence in the mammalian GABAA receptor gene cluster comprising the α1, β2, γ2 and α6 subunits were identified as potential long range transcriptional regulatory components involved in the coordinate regulation of these genes. A region of predicted DNase I hypersensitive sites within the cluster may contain transcriptional regulatory features coordinating gene expression. A novel model is proposed for the coordinate control of the gene cluster and parallel expression of the α1 and β2 subunits, based upon the selective action of putative Scaffold/Matrix Attachment Regions (S/MARs).ConclusionThe putative regulatory features identified by genomic analysis of GABAA receptor genes were substantiated by cross-species comparative analysis and now require experimental verification. The proposed model for the coordinate regulation of genes in the cluster accounts for the head-to-head orientation and parallel expression of the α1 and β2 subunit genes, and for the disruption of transcription caused by insertion of a neomycin gene in the close vicinity of the α6 gene, which is proximal to a putative critical S/MAR.
Highlights
Subtypes of the GABA type A (GABAA) receptor subunit exhibit diverse temporal and spatial expression patterns
The purpose of the current work was to utilise a wide range of promoter prediction software to analyse each mammalian GABAA receptor subunit gene, and to use comparative genomic analysis to further substantiate the predictions made by these tools
The α1 subunit gene is strongly expressed in all brain regions, being a component of the most abundant GABAA receptor subtype, α1β2γ2 [21]
Summary
Subtypes of the GABAA receptor subunit exhibit diverse temporal and spatial expression patterns. The GABA type A (GABAA) synaptic receptor is a ligandgated ion channel (LGIC), an integral membrane protein which mediates fast synaptic transmission. It is a member of a superfamily of synaptic receptors which includes the nicotinic acetylcholine receptors (nAChR). There exist at least 16 GABAA receptor subunit isoforms in mammals, each encoded by a separate gene. These isoforms have been categorised into classes based upon sequence similarity: six in the α subunit class, three β,.
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