SEQUENCING AND PROMOTER ANALYSIS OF THE GENOMIC REGION BETWEEN THE RAT NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR BETA-4 AND ALPHA-3 GENES

Nicotinic acetylcholine receptors (nAChRs) found on neurons are composed of ligand binding (alpha) and structural (beta) subunits. Different combinations of alpha and beta subunits produce nAChR subtypes with different pharmacological and ion-conducting properties. Transcriptional regulation may be an important determinant of receptor subtype in a neuronal population and thus influence transmission through a ganglion or group of neurons in the CNS by controlling the nAChR subtype(s) present. In order to understand the transcriptional regulation of neuronal nAChRs by cell contact and electrical activity, it will be first necessary to identify DNA elements that control the expression of members of this family and to identify factors required for the expression of these genes. In this report we have begun to examine the 5'-flanking region of one member of the nAChR family of genes, alpha 3. We have sequenced the region between the beta 4 and alpha 3 genes and have identified two promoter regions in the beta 4-alpha 3 intergenic region. One region is close to the beta 4 gene downstream of exon 6 and has strong promoter activity in both orientations; the other is close to the start of the alpha 3 gene coding region. A region with putative silencer activity is also found near the upstream promoter. This bidirectional promoter region could be involved in the control of alpha 3 and beta 4 gene expression. (C) 1993 John Wiley & Sons, Inc.