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

Autor: Lassar, Andrew B., Davis, Robert L., Wright, Woodring E., Kadesch, Tom, Murre, Cornelis, Voronova, Anna, Baltimore, David, Weintraub, Harold
Zdroj: Cell; July 1991, Vol. 66 Issue: 2 p305-315, 11p
Abstrakt: 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.
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