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| Status |
Public on Apr 01, 2017 |
| Title |
Epigenetic Profile in Transcription elongation factors are in vivo-specific cancer dependencies in glioma |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Glioblastoma ranks as one of the most lethal human cancers, with no effective therapies. To discover novel therapeutic targets, here we performed parallel in vivo and in vitro RNA interference screens of epigenetic regulators and show that transcription elongation factors are essential for human glioblastoma cell survival in vivo, but not in vitro. Context-specific dependency in vivo is driven by microenvironment-induced global changes in the cancer epigenome. JMJD6, a top in vivo-specific hit, binds at enhancers and correlates with increased transcription of known pause-controlled genes. JMJD6 knockdown in patient-derived glioblastoma cells enhances survival of mice bearing orthotopic tumors. Moreover, elevated levels of JMJD6 alone, as well as transcription elongation factors collectively, informs tumor grade and predicts poor prognosis for patients. Our work provides a rationale for targeting transcription elongation as a therapeutic strategy in glioblastoma and, more broadly, the power of in vivo phenotypic screening to identify therapeutically relevant targets in cancer.
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| Overall design |
H3K27Ac histone modifications and JMJD6 binding were mapped by ChIP-seq in glioblastoma cells grown either in an in vivo intrancranial tumor or in serum free cell culture
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| |
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| Contributor(s) |
Miller TE, Liau B, Bernstein BE, Rich JN |
| Citation(s) |
28678782 |
| Submission date |
Oct 30, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Tyler E Miller |
| Organization name |
Cleveland Clinic Lerner Research Institute
|
| Department |
Stem Cell Biology and Regenerative Medicine
|
| Lab |
Jeremy Rich Lab
|
| Street address |
2111 E 96th Street, NE3-256
|
| City |
Cleveland |
| State/province |
Ohio |
| ZIP/Postal code |
44106 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (17)
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| This SubSeries is part of SuperSeries: |
| GSE74529 |
Transcription elongation factors are in vivo-specific cancer dependencies in glioma |
|
| Relations |
| BioProject |
PRJNA300650 |
| SRA |
SRP065543 |
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