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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 21, 2020 |
| Title |
The oncogenomic function of androgen receptor in esophageal squamous cell carcinoma is directed by GATA3 |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer death worldwide. Emerging evidence suggests that the androgen receptor (AR) is involved in ESCC tumorigenesis. However, how AR exerts its genomic functions in ESCC remains unknown. Here, by defining AR cistromes and analyzing androgen-regulated transcriptomes, we find that AR downregulates the majority of its target genes in ESCC cells. We further find that the pioneer factor GATA3 governs AR-repressed transcription by recruiting SMRT/HDAC3 co-repressors to target gene loci. Importantly, genetic inhibition of GATA3 or pharmacological inhibition of AR/HDAC3 relieves AR-mediated gene repression, leading to ESCC cell growth inhibition in vitro and in vivo. Our findings reveal molecular mechanisms underlying the oncogenomic function of AR in ESCC and identify the GATA3-directed AR transcriptional repression program as a therapeutic target for ESCC.
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| Overall design |
AR cistrome and mRNA profiles of ESCC cells treated with vehicle or R1881 were generated by deep sequencing using Illumina HiSeq4000
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| Contributor(s) |
Chen Z, Huang F, Wang Q |
| Citation(s) |
33139924 |
| Submission date |
Dec 23, 2019 |
| Last update date |
Jan 20, 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) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (30)
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| GSM4231887 |
AR_ChIP_vehicle, rep4 |
| GSM4231888 |
AR_ChIP_R1881, rep1 |
| GSM4231889 |
AR_ChIP_R1881, rep2 |
| GSM4231890 |
AR_ChIP_R1881, rep3 |
| GSM4231891 |
AR_ChIP_R1881, rep4 |
| GSM4231892 |
RNA_vehicle, rep1 |
| GSM4231893 |
RNA_vehicle, rep2 |
| GSM4231894 |
RNA_R1881_4h, rep1 |
| GSM4231895 |
RNA_R1881_4h, rep2 |
| GSM4231896 |
RNA_R1881_24h, rep1 |
| GSM4231897 |
RNA_R1881_24h, rep2 |
| GSM4733283 |
HDAC3_ChIP_vehicle_rep1 |
| GSM4733284 |
HDAC3_ChIP_vehicle_rep2 |
| GSM4733285 |
HDAC3_ChIP_vehicle_rep3 |
| GSM4733286 |
HDAC3_ChIP_vehicle_rep4 |
| GSM4733287 |
HDAC3_ChIP_R1881_rep1 |
| GSM4733288 |
HDAC3_ChIP_R1881_rep2 |
| GSM4733289 |
HDAC3_ChIP_R1881_rep3 |
| GSM4733290 |
HDAC3_ChIP_R1881_rep4 |
| GSM4733291 |
SMART_ChIP_vehicle_rep1 |
| GSM4733292 |
SMART_ChIP_vehicle_rep2 |
| GSM4733293 |
SMART_ChIP_vehicle_rep3 |
| GSM4733294 |
SMART_ChIP_vehicle_rep4 |
| GSM4733295 |
SMART_ChIP_R1881_rep1 |
| GSM4733296 |
SMART_ChIP_R1881_rep2 |
| GSM4733297 |
SMART_ChIP_R1881_rep3 |
| GSM4733298 |
SMART_ChIP_R1881_rep4 |
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| Relations |
| BioProject |
PRJNA597367 |
| SRA |
SRP238627 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE142556_410_N20_r1881.ucsc.bedGraph.gz |
16.7 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE142556_410_N20_v.ucsc.bedGraph.gz |
20.5 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE142556_R-HDAC3.ucsc.bw |
440.8 Mb |
(ftp)(http) |
BW |
| GSE142556_R-SMRT.ucsc.bw |
389.4 Mb |
(ftp)(http) |
BW |
| GSE142556_RAW.tar |
810.0 Kb |
(http)(custom) |
TAR (of TXT) |
| GSE142556_V-HDAC3.ucsc.bw |
438.0 Mb |
(ftp)(http) |
BW |
| GSE142556_V-SMRT.ucsc.bw |
396.4 Mb |
(ftp)(http) |
BW |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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