Abstract

The 5HT3 receptor (5HT3R) is a serotonin-gated ion channel whose expression is restricted to a subset of cells within the central and peripheral nervous systems. In vitro analysis shows that a small proximal region of the TATA-less 5HT3R promoter is sufficient to direct neuronal-specific reporter gene expression. Three potential regulatory elements conserved between the mouse and human genes were identified within this proximal promoter, two of which are known sites for the ubiquitously expressed factors Sp1 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 for neuronal-specific transcriptional activity of the 5HT3R. Furthermore, a complex of neuronal proteins that includes a member(s) of the NF1 family binds to this site, as shown by gel mobility super shift and DNaseI footprinting analyses. Although NF1 has been proposed to mediate basal transcription of many ubiquitously expressed genes, our data suggest that a member of the NF1 transcription factor family participates in neuronal-specific gene expression by promoting interactions with other regulatory factors found in sensory ganglia.

Highlights

  • The 5HT3 receptor (5HT3R) is a serotonin-gated ion channel whose expression is restricted to a subset of cells within the central and peripheral nervous systems

  • nuclear factor 1 (NF1) has been proposed to mediate basal transcription of many ubiquitously expressed genes, our data suggest that a member of the NF1 transcription factor family participates in neuronalspecific gene expression by promoting interactions with other regulatory factors found in sensory ganglia

  • Genomic clones containing the upstream region of the murine and human 5HT3R genes were isolated, and nucleotide sequences were obtained from ϳ2.5 kb of the mouse gene and Ϫ1.8 kb of the human gene upstream of the ATG initiator methionine

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Summary

Introduction

The 5HT3 receptor (5HT3R) is a serotonin-gated ion channel whose expression is restricted to a subset of cells within the central and peripheral nervous systems. In situ hybridization and radioligand binding studies have shown that 5HT3Rs are prominently expressed in a variety of peripheral ganglia, including a subset of neurons within dorsal root, trigeminal, cranial, and enteric ganglia (Tecott et al, 1993, 1995; Johnson and Heinemann, 1995b). As such, this receptor has been proposed to modulate nociception and pain responses, as well as enteric and cardiovascular reflexes.

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