Jl. Bessereau et al., NONMYOGENIC FACTORS BIND NICOTINIC ACETYLCHOLINE-RECEPTOR PROMOTER ELEMENTS REQUIRED FOR RESPONSE TO DENERVATION, The Journal of biological chemistry, 273(21), 1998, pp. 12786-12793
Nicotinic acetylcholine receptors (AChRs) belong to a class of muscle
proteins whose expression is regulated by muscle electrical activity.
In innervated muscle fiber, AChR genes are transcriptionally repressed
outside of the synapse, while after denervation they become reexpress
ed throughout the fiber. The myogenic determination factors (MDFs) of
the MyoD family have been shown to play a central role in this innerva
tion-dependent regulation. In the chicken AChR alpha-subunit gene prom
oter, two E-boxes that bind MDFs are necessary to achieve the enhancem
ent of transcription following muscle denervation. However, the deleti
on of promoter sequences located upstream to these E-boxes greatly imp
airs the response to denervation (Bessereau, J, L,, Stratford-Perricau
det, L, D,, Piette, J,, Le Poupon, C, and Changeux, J, P, (1994) Proc.
Natl Acad. Sci, U, S, A. 91, 1304-1308), Here we identified two addit
ional cia-regulatory elements of the alpha-subunit gene promoter that
cooperate with the E-boxes in the denervation response. One region bin
ds the Sp1 and Sp3 zinc finger transcription factors. The second regio
n binds at least three distinct factors, among which we identified an
upstream stimulatory factor, a b-ZIP-HLH transcription factor. We prop
ose that among MDF-responsive muscle promoters, a specific combination
between myogenic and nonmyogenic factors specify innervation-dependen
t versus innervation-independent promoters.