|
| Status |
Public on Apr 01, 2018 |
| Title |
MEK inhibition rewires enhancer landscapes in RAS-driven Rhabdomyosarcoma to unlock a myogenic differentation block |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Trametinib-treated rhabdomyosarcoma cells undergo transcriptional reprogramming akin to myogenic differentiation. This reprogramming is induced by loss of ERK-mediated inhibition of MYOG expression. Restoration of MYOG allows establishment of super-enhancers at genes expressed by terminally differentiated myotubes. Our findings demonstrate that aberrant MAP kinase activity blocks differentiation in rhabdomyosarcoma and highlight trametinib as a potential therapeutic for RAS-mutated rhabdomyosarcoma.
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| |
|
| Overall design |
RNA-seq in 2 FN-RMS cell lines exposed to either DMSO or Trametinib treatment for various concentrations and timepoints, and siRNA against MEK1 or scramble.
|
| |
|
| Contributor(s) |
Gryder BE, Yohe ME, Wen X |
| Citation(s) |
29973406 |
| |
| Submission date |
Aug 03, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Xinyu Wen |
| E-mail(s) |
wenxi@mail.nih.gov
|
| Phone |
2407606135
|
| Organization name |
NCI, NIH
|
| Department |
Genetics Branch
|
| Lab |
Javed Khan
|
| Street address |
37 Convent Dr.
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (18)
|
| GSM2259162 |
CTR 10 nM Tram, 24 hrs |
| GSM2259163 |
CTR 10 nM Tram, 48 hrs |
| GSM2259164 |
CTR 100 nM Tram, 6 hrs |
| GSM2259165 |
CTR 100 nM Tram, 24 hrs |
| GSM2259166 |
CTR 100 nM Tram, 48 hrs |
| GSM2259167 |
RD si control |
| GSM2259168 |
RD si MEK1 |
| GSM2259169 |
RD untreated |
| GSM2259170 |
RD DMSO |
| GSM2259171 |
RD 10 nM Tram, 6 hrs |
| GSM2259172 |
RD 10 nM Tram, 24 hrs |
| GSM2259173 |
RD 10 nM Tram, 48 hrs |
| GSM2259174 |
RD 100 nM Tram, 6 hrs |
| GSM2259175 |
RD 100 nM Tram, 24 hrs |
| GSM2259176 |
RD 100 nM Tram, 48 hrs |
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| This SubSeries is part of SuperSeries: |
| GSE85171 |
Epigenetic Reprogramming of mutant RAS-driven Rhabdomyosarcoma via MEK Inhibition |
|
| Relations |
| BioProject |
PRJNA336381 |
| SRA |
SRP080882 |
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