Transcriptional control of the neuronal nicotinic acetylcholine receptor gene cluster by the β43′ enhancer, Sp1, SCIP and ETS transcription factors

Receptors assembled from the products of a neuronal beta 4 alpha 3 alpha 5 NAChR gene cluster depend on these genes being coordinately regulated in particular populations of neurons. Little is known, however, about the transcriptional mechanisms that are likely to underlie their co-expression in correct neuronal cell types. We have identified several regulatory elements and transcription factors that influence transcription of the alpha 3 and beta 4 genes. The promoters of these genes appear to contain a common cis element that binds Sp1 transcription factors. They can be activated by the POU-domain factor SCIP and activation does not require SCIP binding sites. Between these two promoters is a cell type specific enhancer called beta 43'. This enhancer has little activity in non-neuronal cells and is preferentially active in particular populations of central neurons. The clustered genes are potential targets of ETS factors as the ETS domain factor, Pet-1 can activate beta 43'-dependent transcription. The neuron-selective properties of beta 43' and its location suggest that it is a component of the cia regulatory information required to control expression of the beta 4 and alpha 3 genes in specific populations of neurons. (C) 2000 Elsevier Science B.V. All rights reserved.