Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo

Andrew B. Lassar, Robert L. Davis, Woodring E. Wright, Tom Kadesch, Cornelis Murre, Anna Voronova, David Baltimore, Harold Weintraub

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Abstract

In this report we provide four lines of evidence indicating that E12/E47-like proteins interact in vivo with the myogenic HLH proteins MyoD and myogenin. First, cotransfection of MyoD and E47 in COS cells indicates that these factors synergistically enhance transcription of a reporter gene containing an oligomerized MyoD-binding site. Second, mobility-shift assays of muscle cell nuclear extracts, "double shifted" with specific antisera, have identified complexes binding to the MEF1 site that contain either MyoD or myogenin in association with El 2/E47-like proteins. Third, association with E47 alters the phosphorylation state of MyoD. Fourth, C3H10T1/2 cells expressing antisense E2A transcripts contain low levels of E2A gene products and display less terminal muscle differentiation when infected with retroviral MyoD or when challenged to differentiate with 5-azacytidine treatment. In addition we demonstrate that MyoD, in conjunction with E12/E47-like proteins, is functioning as a regulatory nodal point for activation of several other downstream muscle regulators.

Original languageEnglish (US)
Pages (from-to)305-315
Number of pages11
JournalCell
Volume66
Issue number2
DOIs
Publication statusPublished - Jul 26 1991

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Lassar, A. B., Davis, R. L., Wright, W. E., Kadesch, T., Murre, C., Voronova, A., ... Weintraub, H. (1991). Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell, 66(2), 305-315. https://doi.org/10.1016/0092-8674(91)90620-E