Abstract
We have investigated the mechanism by which expression of the v-myc oncogene interferes with the competence of primary quail myoblasts to undergo terminal differentiation. Previous studies have established that quail myoblasts transformed by myc oncogenes are severely impaired in the accumulation of mRNAs encoding the myogenic transcription factors Myf-5, MyoD and Myogenin. However, the mechanism responsible for such a repression remains largely unknown. Here we present evidence that v-Myc selectively interferes with quail myoD expression at the transcriptional level. Cis-regulatory elements involved in the auto-activation of qmyoD are specifically targeted in this unique example of transrepression by v-Myc, without the apparent participation of Myc-specific E-boxes or InR sequences. Transiently expressed v-Myc efficiently interfered with MyoD-dependent transactivation of the qmyoD regulatory elements, while the myogenin promoter was unaffected. Finally, we show that forced expression of MyoD in v-myc-transformed quail myoblasts restored myogenin expression and promoted extensive terminal differentiation. These data suggest that transcriptional repression of qmyoD is a major and rate-limiting step in the molecular pathway by which v-Myc severely inhibits terminal differentiation in myogenic cells.
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Acknowledgements
We thank S Alemà (CNR, Roma, Italy) for the adenoviral vectors, D Fischman (Cornell University, New York, USA) for the MF20 antibody, D Gillespie (CRC Beatson Laboratories, Glasgow, UK) for the 237 antibody, E Olson (UT Southwestern Medical Center, Dallas, USA) for the myogenin constructs, B Paterson (NIH, Bethesda, USA) for the anti-Myogenin antibody, G Piaggio (Istituto Regina Elena, Roma, Italy) for the M4 construct and M Zenke (MDC, Berlin, Germany) for the pmycER-ts-sea vector. This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC), MURST (Cofin 1999) and CNR/MURST (Legge 95/95).
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La Rocca, S., Vannucchi, S., Pompili, M. et al. Selective repression of myoD transcription by v-Myc prevents terminal differentiation of quail embryo myoblasts transformed by the MC29 strain of avian myelocytomatosis virus. Oncogene 21, 4838–4842 (2002). https://doi.org/10.1038/sj.onc.1205586
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DOI: https://doi.org/10.1038/sj.onc.1205586