E1A-Mediated Inhibition of Myogenesis Correlates with a Direct Physical Interaction of E1A125 and Basic Helix-Loop-Helix Proteins

Doris A. Taylor, Virginia B. Kraus, John J. Schwarz, Eric N. Olson, William E. Kraus

Research output: Contribution to journalArticle

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Abstract

The observation that adenovirus E1A gene products can inhibit differentiation of skeletal myocytes suggested that E1A may interfere with the activity of myogenic basic helix-loop-helix (bHLH) transcription factors. We have examined the ability of E1A to mediate repression of the muscle-specific creatine kinase (MCK) gene. Both the E1A12S and E1A13S products repressed MCK transcription in a concentration-dependent fashion. In contrast, amino-terminal deletion mutants (d2-36 and d15-35) of E1A12S were defective for repression. E1A12S also repressed expression of a promoter containing a multimer of the MCK high-affinity E box (the consensus site for myogenic bHLH protein binding) that was dependent, in C3H10T1/2 cells, on coexpression of a myogenin bHLH-VP16 fusion protein. A series of coprecipitation experiments with glutathione S-transferase fusion and in vitro-translated proteins demonstrated that E1A12S, but not amino-terminal E1A deletion mutants, could bind to full-length myogenin and E12 and to deletion mutants of myogenin and E12 that spare the bHLH domains. Thus, the bHLH domains of myogenin and E12, and the high-affinity E box, are targets for E1A-mediated repression of the MCK enhancer, and domains of E1A required for repression of muscle-specific gene transcription also mediate binding to bHLH proteins. We conclude that E1A mediates repression of muscle-specific gene transcription through its amino-terminal domain and propose that this may involve a direct physical interaction between E1A and the bHLH region of myogenic determination proteins.

Original languageEnglish (US)
Pages (from-to)4714-4727
Number of pages14
JournalMolecular and Cellular Biology
Volume13
Issue number8
StatePublished - Aug 1993

Fingerprint

MM Form Creatine Kinase
Myogenin
Muscle Development
Helix-Loop-Helix Motifs
Genes
Herpes Simplex Virus Protein Vmw65
Proteins
E-Box Elements
Basic Helix-Loop-Helix Transcription Factors
Muscles
Skeletal Muscle Fibers
Glutathione Transferase
Protein Binding
Adenoviridae

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

E1A-Mediated Inhibition of Myogenesis Correlates with a Direct Physical Interaction of E1A125 and Basic Helix-Loop-Helix Proteins. / Taylor, Doris A.; Kraus, Virginia B.; Schwarz, John J.; Olson, Eric N.; Kraus, William E.

In: Molecular and Cellular Biology, Vol. 13, No. 8, 08.1993, p. 4714-4727.

Research output: Contribution to journalArticle

Taylor, Doris A. ; Kraus, Virginia B. ; Schwarz, John J. ; Olson, Eric N. ; Kraus, William E. / E1A-Mediated Inhibition of Myogenesis Correlates with a Direct Physical Interaction of E1A125 and Basic Helix-Loop-Helix Proteins. In: Molecular and Cellular Biology. 1993 ; Vol. 13, No. 8. pp. 4714-4727.
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