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| Status |
Public on Apr 14, 2017 |
| Title |
Overexpression of c-Myc antagonises transcriptional output of the androgen receptor in prostate cancer [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
c-Myc overexpression LNCaP cells were treated with R1881 or R1881+Doxycycline (to induce c-Myc overexpression) and ChIP-seq studies were performed using antibodies against c-Myc, AR, H3K4me1, H3K4me3, H3K27ac and H3K27m3 Prostate cancer is the most common non-cutaneous cancer in men. The androgen receptor (AR) a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signalling networks have been shown to be altered in patients and to influence AR activity. The oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies, but its impact on AR activity in prostate cancer remains elusive. In this study we assessed the impact of clinically relevant levels of c-Myc overexpression on AR activity and transcriptional output. We found that c-Myc and the AR share a substantial amount of binding sites, which exhibit enhancer-like characteristics. Interestingly, c-Myc overexpression altered global AR chromatin occupancy and antagonised a subset of androgen-induced genes. Furthermore, c-Myc overexpression modified histone marks, most notably H3K4me1 and H3K27me3. Lastly, we validated the antagonistic relationship between c-Myc and two AR target genes, KLK3 and GNMT, in patient samples.
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| Overall design |
ChIP-seq study for c-Myc, AR, H3K4me1, H3K4me3, H3K27ac and H3K27m3 in a c-Myc overexpression LNCaP prostate cell line model (LNCaP MYC) treated with R1881 or R1881+Doxycycline
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| Contributor(s) |
Barfeld SJ, Urbanucci A, Fazli L, Rennie PS, Yegnasubramanian V, de Marzo AM, Thiede B, Harri IM, Hicks JL, Mills IG |
| Citation(s) |
28412251 |
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| Submission date |
Oct 14, 2015 |
| Last update date |
Oct 04, 2022 |
| Contact name |
Alfonso Urbanucci |
| E-mail(s) |
alfonsou@ifi.uio.no
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| Phone |
45048687
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| Organization name |
Oslo University Hospital
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| Street address |
Trondheimsveien 8
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| City |
Oslo |
| State/province |
Oslo |
| ZIP/Postal code |
0560 |
| Country |
Norway |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE73995 |
Overexpression of c-Myc antagonises transcriptional output of the androgen receptor in prostate cancer |
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| Relations |
| BioProject |
PRJNA298682 |
| SRA |
SRP064791 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE73994_RAW.tar |
10.3 Gb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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