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 cel...

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Bibliographic Details
Published in:The Journal of neuroscience 2008-03, Vol.28 (10), p.2459-2470
Main Authors: Camp, Shelley, De Jaco, Antonella, Zhang, Limin, Marquez, Michael, De La Torre, Brian, Taylor, Palmer
Format: Article
Language:English
Subjects:
Acetylcholinesterase - biosynthesis
Acetylcholinesterase - genetics
Animals
Axonal Transport - genetics
Base Sequence
Cell Line
Chick Embryo
Enhancer Elements, Genetic - genetics
Gene Expression Regulation, Enzymologic - physiology
Introns - genetics
Mice
Mice, Knockout
Molecular Sequence Data
Motor Neurons - enzymology
Muscle, Skeletal - enzymology
Neuromuscular Junction - enzymology
Promoter Regions, Genetic - genetics
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Summary: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.
ISSN:0270-6474
1529-2401
1529-2401
DOI:10.1523/JNEUROSCI.4600-07.2008