E1A-mediated inhibition of myogenesis correlates with a direct physical interaction of E1A(12S) 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

48 Scopus citations

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 E1A(12S) and E1A(13S) products repressed MCK transcription in a concentration-dependent fashion. In contrast, amino-terminal deletion mutants (d2-36 and d15-35) of E1A(12S) were defective for repression. E1A(12S) 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 E1A(12S), 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
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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