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 β4α3α5 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 α3 and β4 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 β43'. 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 β43'-dependent transcription. The neuron-selective properties of β43' and its location suggest that it is a component of the cis regulatory information required to control expression of the β4 and α3 genes in specific populations of neurons. Copyright (C) 2000 Elsevier Science B.V.