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| Status |
Public on Aug 29, 2013 |
| Title |
Comparison of Genome-Wide Binding of MyoD in Normal Human Myogenic Cells and Rhabdomyosarcomas Identifies Regional and Local Suppression of Promyogenic Transcription Factors (MyoD ChIP-Seq profiling) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Rhabdomyosarcoma is a pediatric tumor of skeletal muscle that expresses the myogenic basic helix-loop-helix protein MyoD but fails to undergo terminal differentiation. Prior work has determined that DNA binding by MyoD occurs in the tumor cells, but myogenic targets fail to activate. Using MyoD chromatin immunoprecipitation coupled to high-throughput sequencing and gene expression analysis in both primary human muscle cells and RD rhabdomyosarcoma cells, we demonstrate that MyoD binds in a similar genome-wide pattern in both tumor and normal cells but binds poorly at a subset of myogenic genes that fail to activate in the tumor cells. Binding differences are found both across genomic regions and locally at specific sites that are associated with binding motifs for RUNX1, MEF2C, JDP2, and NFIC. These factors are expressed at lower levels in RD cells than muscle cells and rescue myogenesis when expressed in RD cells. MEF2C is located in a genomic region that exhibits poor MyoD binding in RD cells, whereas JDP2 exhibits local DNA hypermethylation in its promoter in both RD cells and primary tumor samples. These results demonstrate that regional and local silencing of differentiation factors contributes to the differentiation defect in rhabdomyosarcomas.
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| |
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| Overall design |
ChIP-Seq profiling of MyoD in human myotube, myoblast and rhabdomyosarcoma cells
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| |
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| Contributor(s) |
MacQuarrie KL, Yao Z, Fong AP, Diede SJ, Rudzinski ER, Hawkins DS, Tapscott SJ |
| Citation(s) |
23230269 |
| Submission date |
Aug 28, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Stephen Tapscott |
| E-mail(s) |
stapscot@fredhutch.org
|
| Organization name |
Fred Hutch Cancer Research Center
|
| Department |
Human Biology
|
| Lab |
Tapscott
|
| Street address |
1100 Fairview N. Ave
|
| City |
Seattle |
| State/province |
WASHINGTON |
| ZIP/Postal code |
98103 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE50415 |
Comparison of Genome-Wide Binding of MyoD in Normal Human Myogenic Cells and Rhabdomyosarcomas Identifies Regional and Local Suppression of Promyogenic Transcription Factors |
|
| Relations |
| BioProject |
PRJNA217446 |
| SRA |
SRP029295 |
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