|
| Status |
Public on Apr 02, 2012 |
| Title |
miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells (Illumina) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Background: Similar to replicating myoblasts, many rhabdomyosarcoma cells express the myogenic determination gene MyoD. In contrast to myoblasts, rhabdomyosarcoma cells do not make the transition from a regulative growth phase to terminal differentiation. Previously we demonstrated that the forced expression of MyoD with its E-protein dimerization partner was sufficient to induce differentiation and suppress multiple growth-promoting genes, suggesting that the dimer was targeting a switch that regulated the transition from growth to differentiation. Our data also suggested that a balance existed between various inhibitory transcription factors and MyoD activity that kept rhabdomyosarcomas trapped in a proliferative state. Methods: Potential myogenic co-factors identified by analysis of high-throughput sequencing of chromatin immunoprecipitation experiments in normal myogenic cells were tested for their ability to drive differentiation in rhabdomyosarcoma cell culture models, and their relation to MyoD activity determined through molecular biological experiments. Results: Modulation of the transcription factors RUNX1 and ZNF238, factors with poorly delineated roles in myogenic development, can induce differentiation in rhabdomyosarcoma cells and their activity is integrated, at least in part, through the activation of miR-206, which acts as a genetic switch to transition the cell from a proliferative growth phase to differentiation. The inhibitory transcription factor MSC also plays a role in controlling miR-206, appearing to function by occluding a binding site for MyoD in the miR-206 promoter. Conclusions: These findings suggest that nested feed-forward circuits that proceed from MyoD, to RUNX1, to ZNF238, and finally to miR-206 function in both rhabdomyosarcomas as well as normal myogenesis to control the decision point of proliferation versus differentiation.
|
| |
|
| Overall design |
Total RNA samples were collected from human RD cells transduced with lentivirus carrying RUNX1, RP58 (ZNF238), miR-206 or GFP (three biological replicates each) and allowed to differentiate for 72 hours.
|
| |
|
| Contributor(s) |
MacQuarrie KL, Yao Z, Young JM, Cao Y, Tapscott SJ |
| Citation(s) |
22541669 |
| Submission date |
Feb 01, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Janet M. Young |
| E-mail(s) |
jayoung@fhcrc.org
|
| Phone |
206 667 1471
|
| Organization name |
Fred Hutchinson Cancer Research Center
|
| Department |
Division of Human Biology
|
| Lab |
Tapscott
|
| Street address |
1100 Fairview Avenue N., C3-168, P.O. Box 19024
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE35921 |
miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells |
|
| Relations |
| BioProject |
PRJNA156101 |
Less...
More...