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| Status |
Public on May 31, 2018 |
| Title |
Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting therapies, how AR-V7 mediates genomic functions in CRPC remains largely unknown. Using a ChIP-exo approach, we show AR-V7 binds to distinct genomic regions and recognizes a full-length androgen-responsive element in CRPC cells and patient tissues. Remarkably, we find dramatic differences in AR-V7 cistromes across diverse CRPC cells and patient tissues, regulating different target gene sets involved in CRPC progression. Surprisingly, we discover that HoxB13 is universally required for and colocalizes with AR-V7 binding to open chromatin across CRPC genomes. HoxB13 pioneers AR-V7 binding through direct physical interaction, and collaborates with AR-V7 to up-regulate target oncogenes. Transcriptional coregulation by HoxB13 and AR-V7 was further supported by their coexpression in tumors and circulating tumor cells from CRPC patients. Importantly, HoxB13 silencing significantly decreases CRPC growth through inhibition of AR-V7 oncogenic function. These results identify HoxB13 as a pivotal upstream regulator of AR-V7-driven transcriptomes that are often cell context-dependent in CRPC, suggesting that HoxB13 may serve as a therapeutic target for AR-V7-driven prostate tumors.
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| Overall design |
To identify AR-V7 and HoxB13 binding sites in CRPC, ChIP-exo and ATAC-seq were performed in CRPC cells and tissues. RNA-seq was performed to examine AR-V7 and HoxB13 regulated profiles. Each experiment includes two biological replicates.
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| Contributor(s) |
Chen Z, Wang Q |
| Citation(s) |
29844167 |
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| Submission date |
May 29, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Zhong Chen |
| E-mail(s) |
zhong.chen128@duke.edu
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| Organization name |
Duke University
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| Department |
Pathology
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| Lab |
Room 1027B, GSRB1
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| Street address |
905 S. LaSalle Street
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| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27710 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (40)
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| GSM2643239 |
22RV1_V7_ChIPexo, Biological replicate 1 |
| GSM2643240 |
22RV1_V7_ChIPexo, Biological replicate 2 |
| GSM2643241 |
22RV1_C19_ChIPexo, Biological replicate 1 |
| GSM2643242 |
22RV1_C19_ChIPexo, Biological replicate 2 |
| GSM2643243 |
22RV1_HoxB13_ChIPexo, Biological replicate 1 |
| GSM2643244 |
22RV1_HoxB13_ChIPexo, Biological replicate 2 |
| GSM2643245 |
LN95_V7_ChIPexo, Biological replicate 1 |
| GSM2643246 |
LN95_V7_ChIPexo, Biological replicate 2 |
| GSM2643247 |
LN95_C19_ChIPexo, Biological replicate 1 |
| GSM2643248 |
LN95_C19_ChIPexo, Biological replicate 2 |
| GSM2643249 |
LN95_HoxB13_ChIPexo, Biological replicate 1 |
| GSM2643250 |
LN95_HoxB13_ChIPexo, Biological replicate 2 |
| GSM2643251 |
22RV1_siControl_RNAseq, Biological replicate 1 |
| GSM2643252 |
22RV1_siControl_RNAseq, Biological replicate 2 |
| GSM2643253 |
22RV1_siAR-V7_RNAseq, Biological replicate 1 |
| GSM2643254 |
22RV1_siAR-V7_RNAseq, Biological replicate 2 |
| GSM2643255 |
22RV1_siHoxB13_RNAseq, Biological replicate 1 |
| GSM2643256 |
22RV1_siHoxB13_RNAseq, Biological replicate 2 |
| GSM2643257 |
LN95_siControl_RNAseq, Biological replicate 1 |
| GSM2643258 |
LN95_siControl_RNAseq, Biological replicate 2 |
| GSM2643259 |
LN95_siAR-V7_RNAseq, Biological replicate 1 |
| GSM2643260 |
LN95_siAR-V7_RNAseq, Biological replicate 2 |
| GSM2643261 |
LN95_siHoxB13_RNAseq, Biological replicate 1 |
| GSM2643262 |
LN95_siHoxB13_RNAseq, Biological replicate 2 |
| GSM2643263 |
A17_HoxB13_ChIPexo |
| GSM2643264 |
A17_V7_ChIPexo |
| GSM2643265 |
A31_HoxB13_ChIPexo |
| GSM2643266 |
A31_V7_ChIPexo |
| GSM2643267 |
A3_HoxB13_ChIPexo |
| GSM2643268 |
A3_V7_ChIPexo |
| GSM2643269 |
A17_RNAseq, Biological replicate 1 |
| GSM2643270 |
A17_RNAseq, Biological replicate 2 |
| GSM2643271 |
A31_RNAseq, Biological replicate 1 |
| GSM2643272 |
A31_RNAseq, Biological replicate 2 |
| GSM2643273 |
A3_RNAseq, Biological replicate 1 |
| GSM2643274 |
A3_RNAseq, Biological replicate 2 |
| GSM3075371 |
22RV1_ATAC_seq rep1 |
| GSM3075372 |
22RV1_ATAC_seq rep2 |
| GSM3075373 |
LN95_ATAC_seq rep1 |
| GSM3075374 |
LN95_ATAC_seq rep2 |
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| Relations |
| BioProject |
PRJNA388315 |
| SRA |
SRP108215 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99378_A17_HoxB13.bw |
1.5 Gb |
(ftp)(http) |
BW |
| GSE99378_A17_V7.bw |
1.3 Gb |
(ftp)(http) |
BW |
| GSE99378_A31_HoxB13.bw |
1.5 Gb |
(ftp)(http) |
BW |
| GSE99378_A31_V7.bw |
1.2 Gb |
(ftp)(http) |
BW |
| GSE99378_A3_HoxB13.bw |
1.3 Gb |
(ftp)(http) |
BW |
| GSE99378_A3_V7.bw |
1.1 Gb |
(ftp)(http) |
BW |
| GSE99378_CW22RV1_vehicle_C19.bw |
1.3 Gb |
(ftp)(http) |
BW |
| GSE99378_CW22RV1_vehicle_Hox.bw |
938.2 Mb |
(ftp)(http) |
BW |
| GSE99378_CW22RV1_vehicle_V7.bw |
1.1 Gb |
(ftp)(http) |
BW |
| GSE99378_LN95_c19.bw |
1.6 Gb |
(ftp)(http) |
BW |
| GSE99378_LN95_hox.bw |
1.3 Gb |
(ftp)(http) |
BW |
| GSE99378_LN95_v7.1.bw |
1.1 Gb |
(ftp)(http) |
BW |
| GSE99378_RAW.tar |
1.9 Gb |
(http)(custom) |
TAR (of BEDGRAPH) |
| GSE99378_RNAseq_22RV1_gene.read.counts.txt.gz |
365.4 Kb |
(ftp)(http) |
TXT |
| GSE99378_RNAseq_A17_gene.read.counts.txt.gz |
85.8 Kb |
(ftp)(http) |
TXT |
| GSE99378_RNAseq_A31_gene.read.counts.txt.gz |
80.1 Kb |
(ftp)(http) |
TXT |
| GSE99378_RNAseq_A3_gene.read.counts.txt.gz |
91.6 Kb |
(ftp)(http) |
TXT |
| GSE99378_RNAseq_LN95_gene.read.counts.txt.gz |
355.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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