Acetylcholinesterase expression in muscle is specifically controlled by a promoter-selective enhancesome in the first intron.
Mammalian acetylcholinesterase (AChE) gene expression is exquisitely regulated in target tissues and cells during differentiation. An intron located between the first and second exons governs a approximately 100-fold increase in AChE expression during myoblast to myotube differentiation in C2C12 cells. Regulation is confined to 255 bp of evolutionarily conserved sequence containing functional transcription factor consensus motifs that indirectly interact with the endogenous promoter. To examine control in vivo, this region was deleted by homologous recombination. The knock-out mouse is virtually devoid of AChE activity and its encoding mRNA in skeletal muscle, yet activities in brain and spinal cord innervating skeletal muscle are unaltered. The transcription factors MyoD and myocyte enhancer factor-2 appear to be responsible for muscle regulation. Selective control of AChE expression by this region is also found in hematopoietic lineages. Expression patterns in muscle and CNS neurons establish that virtually all AChE activity at the mammalian neuromuscular junction arises from skeletal muscle rather than from biosynthesis in the motoneuron cell body and axoplasmic transport.
Camp
Shelley
S
Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093-0650, USA.
De Jaco
Antonella
A
Zhang
Limin
L
Marquez
Michael
M
De la Torre
Brian
B
Taylor
Palmer
P
D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007438:Introns / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology*; D009469:Neuromuscular Junction / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000235:genetics*
D000110:Acetylcholinesterase