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| Status |
Public on Jan 04, 2018 |
| Title |
LNCaP treated with iBET |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
BRD4 belongs to the bromodomain and extraterminal (BET) family of epigenetic reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We define a new function for BRD4 that is distinct from its established role in transcriptional gene regulation. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs), and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex. Loss of BRD4 function blocks the recruitment of multiple DNA repair proteins to the chromatin upon DNA damage, and thereby results in defective DNA repair. In support of this, we also show that in clinical tumor samples, BRD4 protein levels are negatively associated with outcome after prostate cancer (PCa) radiation therapy. Thus, in addition to regulating gene-expression, BRD4 is also a central player in the repair of DNA breaks, with significant implications for cancer therapy.
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| Overall design |
LNCaP cellline treated iBET at two different doses with duplicates
6 samples including 2 (replicates) LNCaP cell line treated with DMSO, 2 (replicates) LNCaP treated with iBET at 0.5uM, and 2 (replicates) LNCaP treated with iBET at 2uM for 8 hours
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| Contributor(s) |
Yuan W, Welti J, Sharp A, deBono J |
| Citation(s) |
29346775 |
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| Submission date |
Sep 15, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Wei Yuan |
| E-mail(s) |
wei.yuan@icr.ac.uk
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| Organization name |
Institute of Cancer Research
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| Street address |
15 Cotswold Road
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| City |
Sutton, London |
| ZIP/Postal code |
SM2 5NG |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| GSM2788088 |
LNCaP treated with 2uM iBET for 8 hours_1 |
| GSM2788089 |
LNCaP treated with 2uM iBET for 8 hours_2 |
| GSM2788090 |
LNCaP treated with 0.5uM iBET for 8 hours_1 |
| GSM2788091 |
LNCaP treated with 0.5uM iBET for 8 hours_2 |
| GSM2788092 |
LNCaP treated with DMSO for 8 hours_1 |
| GSM2788093 |
LNCaP treated with DMSO for 8 hours_2 |
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| Relations |
| BioProject |
PRJNA408077 |
| SRA |
SRP118294 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE103907_RAW.tar |
91.1 Mb |
(http)(custom) |
TAR (of GTF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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