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 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.
journal_name
Elifejournal_title
eLifeauthors
Tenente IM,Hayes MN,Ignatius MS,McCarthy K,Yohe M,Sindiri S,Gryder B,Oliveira ML,Ramakrishnan A,Tang Q,Chen EY,Petur Nielsen G,Khan J,Langenau DMdoi
10.7554/eLife.19214subject
Has Abstractpub_date
2017-01-12 00:00:00issn
2050-084Xjournal_volume
6pub_type
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