T. Sunyer et Jp. Merlie, CELL TYPE-DEPENDENT AND DIFFERENTIATION-DEPENDENT EXPRESSION FROM THEMOUSE ACETYLCHOLINE-RECEPTOR EPSILON-SUBUNIT PROMOTER, Journal of neuroscience research, 36(2), 1993, pp. 224-234
The nicotinic acetylcholine receptor (AChR) in adult skeletal muscle i
s composed of alpha-, beta-, epsilon-, and delta-subunits and is local
ized at the neuromuscular junction; in contrast, the more diffusely di
stributed fetal form is composed of alpha-, beta-, gamma-, and delta-s
ubunits. To define sequences necessary for the transcriptional regulat
ion of the mouse epsilon-subunit gene, we sequenced and analyzed 1036
bp upstream of the transcription start site. Using deletion analysis o
f the 5'-flanking region linked to the bacterial chloramphenicol acety
ltransferase (CAT) gene and transfection of the resulting constructs i
nto established cell lines, we demonstrate that a 151 bp fragment exhi
bits cell type- and differentiation-specific promoter activity. This a
ctivity was independent of a myogenic factor putative binding site (E-
box). However, transactivation experiments with recombinant myoD, myog
enin, or MRF4 showed that the E-box was functional and that MRF4 prefe
rentially transactivates the epsilon-promoter. Thus, like other AChR p
romoters, the proximal region of the epsilon-promoter contains informa
tion for cell type-specific and developmental regulation of CAT and ca
n be transactivated by myogenic factors in cultured cell lines. Unlike
the other AChR promoters characterized to date, epsilon-promoter func
tion can be partially independent of myogenic factors of the helix-loo
p-helix class. (C) 1993 Wiley-Liss, Inc.