The Journal of Neuroscience, August 15, 1998, 18(16):6186-6194
Neuronal Expression of the 5HT3 Serotonin Receptor
Gene Requires Nuclear Factor 1 Complexes
Fiona K.
Bedford1,
David
Julius2, and
Holly A.
Ingraham1
Departments of 1 Physiology and 2 Cellular
and Molecular Pharmacology, University of California at San Francisco,
San Francisco, California 94143-0444
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.
Key words:
gene expression; sensory neuron; NF1 transcription
factor; ligand-gated ion channel; 5HT3R; TATA-less
promoter
Copyright © 1998 Society for Neuroscience 0270-6474/98/18166186-09$05.00/0
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