Neuronal nicotinic acetylcholine receptors (nAChR) are expressed at specifi
c times during development and in discrete neuronal populations. Transcript
ional regulation of the receptor genes clearly plays a key role in the mole
cular pathway underlying the expression of these critical synaptic componen
ts. In an effort to understand this regulation, we focus upon the genes enc
oding three receptor subunits: alpha3, alpha5 and beta4. These subunits are
genomically clustered and constitute the predominant nAChR subtype express
ed in the peripheral nervous system. We and others demonstrated that the ge
neral transcription factors, Sp1 and Sp3, can transactivate the promoter of
each subunit gene. Further, we showed that the regulatory factor Sox10 tra
nsactivates the alpha3 and beta4 promoters and does so in a cell-type-speci
fic manner. Interestingly, the Sp- and Sox10-binding sites on the beta4 pro
moter are located immediately adjacent to each other, raising the possibili
ty that the two sets of factors functionally interact to regulate receptor
gene expression. Consistent with this hypothesis, we demonstrated that the
proteins can directly interact. Here, we extend these observations and show
that Sox10 and the Sp factors functionally interact, leading to synergisti
c transcriptional activation in a cholinergic cell Line. Finally, evidence
for the existence of cell-type-specific co-regulators for Sp1 and Sox10 is
presented. (C) 2000 Elsevier Science Ltd. All rights reserved.