Characterization of a muscle-specific enhancer in human MuSK promoter reveals the essential role of myogenin in controlling activity-dependent gene regulation. J Biol Chem 2006 Feb 17;281(7):3943-53
Date
12/20/2005Pubmed ID
16361705DOI
10.1074/jbc.M511317200Scopus ID
2-s2.0-33645217321 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
Neuromuscular synaptogenesis is initiated by the release of agrin from motor neurons and the activation of the receptor tyrosine kinase, MuSK, in the postsynaptic membrane. MuSK gene expression is regulated by nerve-derived agrin and muscle activity. Agrin stimulates synapse-specific MuSK gene expression by activating GABP(alphabeta) transcription factors in endplate-associated myonuclei. In contrast, the mechanism by which muscle activity regulates MuSK gene expression is not known. We report on a 60-bp MuSK enhancer that confers promoter regulation by muscle differentiation, changes in intracellular calcium, and muscle activity. Within this enhancer, we identified a single E-box that is essential for this regulation. This E-box binds myogenin, and we showed that myogenin is necessary for not only MuSK but also nAChR gene regulation by muscle activity. Surprisingly, the same E-box functions in vivo to mediate muscle-specific and differentiation-dependent gene induction in zebrafish, suggesting an evolutionary conserved mechanism of regulation of synaptic protein gene expression.
Author List
Tang H, Veldman MB, Goldman DAuthor
Matthew B. Veldman PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Calcium
Cell Differentiation
Cells, Cultured
Enhancer Elements, Genetic
Gene Expression Regulation
Humans
Molecular Sequence Data
Muscle, Skeletal
Myogenin
Promoter Regions, Genetic
Receptor Protein-Tyrosine Kinases
Receptors, Cholinergic
Receptors, Nicotinic
Transcriptional Activation
Zebrafish
