Transcriptional control of the neuronal nicotinic acetylcholine receptor gene cluster by the beta43' enhancer, Sp1, SCIP and ETS transcription factors.
Receptors assembled from the products of a neuronal beta4alpha3alpha5 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 alpha3 and beta4 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 beta43'. 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 beta43'-dependent transcription. The neuron-selective properties of beta43' and its location suggest that it is a component of the cis regulatory information required to control expression of the beta4 and alpha3 genes in specific populations of neurons.
Deneris
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ES
Case Western Reserve University, School of Medicine, Department of Neurosciences, Cleveland OH 44106-4975, USA. esd@po.cwru.edu
Francis
N
N
McDonough
J
J
Fyodorov
D
D
Miller
T
T
Yang
X
X
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000502:physiology; D050816:Octamer Transcription Factor-6; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
C494179:Pou3f1 protein, rat; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011978:Receptors, Nicotinic; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6