ZFIN ID: ZDB-PUB-170113-1
Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma
Tenente, I.M., Hayes, M.N., Ignatius, M.S., McCarthy, K., Yohe, M., Sindiri, S., Gryder, B., Oliveira, M.L., Ramakrishnan, A., Tang, Q., Chen, E.Y., Petur Nielsen, G., Khan, J., Langenau, D.M.
Date: 2017
Source: eLIFE   6: (Journal)
Registered Authors: Hayes, Madeline, Ignatius, Myron, Langenau, David, Tang, Qin
Keywords: cancer biology, developmental biology, human, muscle, myf5, myoD, rhabdomyosarcoma, stem cells, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Chromatin Immunoprecipitation
  • Humans
  • MyoD Protein/metabolism*
  • Myogenic Regulatory Factor 5/metabolism*
  • Rhabdomyosarcoma/physiopathology*
  • Sequence Analysis, DNA
  • Transcription, Genetic*
  • Zebrafish
PubMed: 28080960 Full text @ Elife
Rhabdomyosarcoma (RMS) is a pediatric malignacy of muscle with myogenic regulatory transcription factors MYOD and MYF5 being expressed in this disease. Consensus in the field has been that expression of these factors likely reflects the target cell of transformation rather than being required for continued tumor growth. Here, we used a transgenic zebrafish model to show that Myf5 is sufficient to confer tumor-propagating potential to RMS cells and caused tumors to initiate earlier and have higher penetrance. Analysis of human RMS revealed that MYF5 and MYOD are mutually-exclusively expressed and each is required for sustained tumor growth. ChIP-seq and mechanistic studies in human RMS uncovered that MYF5 and MYOD bind common DNA regulatory elements to alter transcription of genes that regulate muscle development and cell cycle progression. Our data support unappreciated and dominant oncogenic roles for MYF5 and MYOD convergence on common transcriptional targets to regulate human RMS growth.