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Status |
Public on Feb 19, 2017 |
Title |
Polycomb-mediated deactivation of AR-feedback loop leads to castration-resistant prostate cancer [ChIP-seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Castration-resistant prostate cancer (CRPC) is a lethal disease, often characterized by aberrant androgen receptor (AR) activation independently of androgen. We have previously reported that AR can directly repress the expression of many target genes, one of which is NOV/CCN3. Here we show that NOV, primarily localized in the cytoplasm, physically interacts with AR at its Nterminus and sequesters AR and AR variants in the cytoplasm, thereby reducing AR chromatintargeting. This negative feedback loop, however, is disrupted in CRPC due to epigenetic silencing of NOV by the Polycomb group protein EZH2, rendering AR transcriptional activities and drug-resistant prostate cancer progression. Our findings thus suggest a working model wherein AR-repressed genes critically prevent CRPC through negative feedback loops inhibiting AR signaling.
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Overall design |
ChIP_Seq examination of AR and NOV binding sites in LNCaP cells
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Contributor(s) |
Yu J, Fong K, Zhao J |
Citation(s) |
27815387 |
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Submission date |
Mar 17, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Jindan Yu |
E-mail(s) |
jindan.yu@emory.edu
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Organization name |
Emory University
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Department |
Urology
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Lab |
Jindan Yu's lab
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Street address |
E330, 1760 Haygood Dr NE
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City |
Atlanta |
State/province |
GA |
ZIP/Postal code |
30322 |
Country |
USA |
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Platforms (1) |
GPL15456 |
Illumina HiScanSQ (Homo sapiens) |
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Samples (3) |
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This SubSeries is part of SuperSeries: |
GSE79358 |
Polycomb-mediated deactivation of AR-feedback loop leads to castration-resistant prostate cancer |
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Relations |
BioProject |
PRJNA315572 |
SRA |
SRP071950 |
Supplementary file |
Size |
Download |
File type/resource |
GSE79357_RAW.tar |
102.5 Mb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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