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Series GSE74520 Query DataSets for GSE74520
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
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.
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
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
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (17)
GSM1922075 IN528ic H3K27Ac
GSM1922076 IN528ic JMJD6
GSM1922077 IN528ic input
This SubSeries is part of SuperSeries:
GSE74529 Transcription elongation factors are in vivo-specific cancer dependencies in glioma
BioProject PRJNA300650
SRA SRP065543

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Supplementary file Size Download File type/resource
GSE74520_RAW.tar 2.6 Gb (http)(custom) TAR (of BED, BIGWIG, TDF)
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Raw data are available in SRA
Processed data provided as supplementary file

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