PUBLICATION

Characterization of a muscle-specific enhancer in human MuSK promoter reveals the essential role of myogenin in controlling activity-dependent gene regulation

Authors
Tang, H., Veldman, M.B., and Goldman, D.
ID
ZDB-PUB-051221-2
Date
2006
Source
The Journal of biological chemistry   281(7): 3943-3953 (Journal)
Registered Authors
Goldman, Dan, Veldman, Matt
Keywords
none
MeSH Terms
  • Animals
  • Base Sequence
  • Calcium/physiology
  • Cell Differentiation
  • Cells, Cultured
  • Enhancer Elements, Genetic/physiology*
  • Gene Expression Regulation*
  • Humans
  • Molecular Sequence Data
  • Muscle, Skeletal/metabolism*
  • Myogenin/physiology*
  • Promoter Regions, Genetic*
  • Receptor Protein-Tyrosine Kinases/genetics*
  • Receptors, Cholinergic/genetics*
  • Receptors, Nicotinic/genetics
  • Transcriptional Activation
  • Zebrafish/metabolism
PubMed
16361705 Full text @ J. Biol. Chem.
Abstract
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 transcription factors in endplate-associated myonuclei. In contrast the mechanism by which muscle activity regulates MuSK gene expression is not known. Here 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 show 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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping