PUBLICATION

Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma

Authors
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.
ID
ZDB-PUB-170113-1
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
  • Chromatin Immunoprecipitation
  • Rhabdomyosarcoma/physiopathology*
  • Zebrafish
  • Animals, Genetically Modified
  • Animals
  • Humans
  • Transcription, Genetic*
  • MyoD Protein/metabolism*
  • Sequence Analysis, DNA
  • Myogenic Regulatory Factor 5/metabolism*
(all 10)
PubMed
28080960 Full text @ Elife
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.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Human Disease / Model
Human Disease Fish Conditions Evidence
embryonal rhabdomyosarcomaTAS
1 - 1 of 1
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Sequence Targeting Reagents
No data available
Fish
Fish
cz3327Tg; zf38Tg (AB)
rag2fb101/fb101
1 - 2 of 2
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Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
mCherryEFGmCherry
1 - 2 of 2
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Mapping
No data available
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Citation
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. (2017) Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. eLIFE. 6.