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The Journal of Neuroscience, March 5, 2008, 28(10):2459-2470; doi:10.1523/JNEUROSCI.4600-07.2008

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Cellular/Molecular
Acetylcholinesterase Expression in Muscle Is Specifically Controlled by a Promoter-Selective Enhancesome in the First Intron

Shelley Camp, Antonella De Jaco, Limin Zhang, Michael Marquez, Brian De La Torre, and Palmer Taylor

Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093-0650

Correspondence should be addressed to Palmer Taylor, Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093-0650. Email: pwtaylor{at}ucsd.edu

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 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.

Key words: enhancesome; myogenesis; knock-out mouse; acetylcholinesterase; differentiation; muscle

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Received Oct. 9, 2007; revised Jan. 9, 2008; accepted Jan. 17, 2008.

Correspondence should be addressed to Palmer Taylor, Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093-0650. Email: pwtaylor{at}ucsd.edu

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				A. Dobbertin, A. Hrabovska, K. Dembele, S. Camp, P. Taylor, E. Krejci, and V. Bernard Targeting of Acetylcholinesterase in Neurons In Vivo: A Dual Processing Function for the Proline-Rich Membrane Anchor Subunit and the Attachment Domain on the Catalytic Subunit J. Neurosci., April 8, 2009; 29(14): 4519 - 4530. [Abstract] [Full Text] [PDF]

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