An E box mediates activation and repression of the acetylcholine receptor δ-subunit gene during myogenesis

Alex Simon, Steven J. Burden

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The genes encoding the skeletal muscle acetylcholine receptor (AChR) are induced during muscle development and are regulated subsequently by innervation. Because both the initiation and the subsequent regulation of AChR expression are controlled by transcriptional mechanisms, an understanding of the steps that regulate AChR expression following innervation is likely to require knowledge of the pathway that activates AChR genes during myogenesis. Thus, we sought to identify the cis-acting sequences that regulate expression of the AChR δ-subunit gene during muscle differentiation. We transfected muscle and nonmuscle cell lines with gene fusions between 5′-flanking DNA from the AChR δ-subunit gene and the human growth hormone gene, and we show here that 148 bp of 5′-flanking DNA from the AChR δ-subunit gene contains two regulatory elements that control muscle-specific gene expression. One element is an E box, which is important both for activation of the δ-subunit gene in myotubes and for its repression in myoblasts and nonmuscle cells. Mutation of this E box, which prevents binding of MyoD-E2A and myogenin-E2A heterodimers, decreases expression in myotubes and increases expression in myoblasts and nonmuscle cells. An E-box binding activity, which does not contain MyoD, myogenin, or E2A proteins, is present in muscle and nonmuscle cells and may be responsible for repressing the δ-subunit gene in myoblasts and nonmuscle cells. An enhancer, which lacks E boxes, is also required for expression of the δ-subunit gene but does not confer muscle-specific expression.

Original languageEnglish (US)
Pages (from-to)5133-5140
Number of pages8
JournalMolecular and Cellular Biology
Volume13
Issue number9
StatePublished - Sep 1993
Externally publishedYes

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Muscle Development
Cholinergic Receptors
Myoblasts
Genes
Myogenin
Skeletal Muscle Fibers
Muscles
Muscle Cells
E-Box Elements
Gene Expression
Human Growth Hormone
Gene Fusion
Transcriptional Activation
Skeletal Muscle
Cell Line
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

An E box mediates activation and repression of the acetylcholine receptor δ-subunit gene during myogenesis. / Simon, Alex; Burden, Steven J.

In: Molecular and Cellular Biology, Vol. 13, No. 9, 09.1993, p. 5133-5140.

Research output: Contribution to journalArticle

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