Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma

Inês M. Tenente, Madeline N. Hayes, Myron S. Ignatius, Karin McCarthy, Marielle Yohe, Sivasish Sindiri, Berkley Gryder, Mariana L. Oliveira, Ashwin Ramakrishnan, Qin Tang, Eleanor Y. Chen, G. Petur Nielsen, Javed Khan, David M. Langenau

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 MYODare 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.

Original languageEnglish (US)
Article numbere19214
JournaleLife
Volume6
DOIs
StatePublished - Jan 12 2017
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    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., Nielsen, G. P., Khan, J., & Langenau, D. M. (2017). Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. eLife, 6, [e19214]. https://doi.org/10.7554/eLife.19214