NEURONAL EXPRESSION OF THE 5HT(3) SEROTONIN RECEPTOR GENE REQUIRES NUCLEAR FACTOR-1 COMPLEXES

The 5HT(3) receptor (5HT(3)R) is a serotonin-gated ion channel whose e xpression is restricted to a subset of cells within the central and pe ripheral nervous systems. In vitro analysis shows that a small proxima l region of the TATA-less 5HT(3)R promoter is sufficient to direct neu ronal-specific reporter gene expression. Three potential regulatory el ements conserved between the mouse and human genes were identified wit hin this proximal promoter, two of which are known sites for the ubiqu itously expressed factors Spl and nuclear factor 1 (NF1), Surprisingly , mutation of the NF1 binding site abolished all reporter activity in cell transfection studies, suggesting that this element is essential f or neuronal-specific transcriptional activity of the 5HT(3)R. Furtherm ore, a complex of neuronal proteins that includes a member(s) of the N F1 family binds to this site, as shown by gel mobility super shift and DNaseI footprinting analyses, Although NF1 has been proposed to media te basal transcription of many ubiquitously expressed genes, our data suggest that a member of the NF1 transcription factor family participa tes in neuronal-specific gene expression by promoting interactions wit h other regulatory factors found in sensory ganglia.