NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE80742 Query DataSets for GSE80742
Status Public on Mar 07, 2018
Title Identification and characterization of androgen receptor splice variants preferred bindings that drive prostate cancer progression [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Androgen receptor (AR) splice variants (ARVs) are implicated in developing castration-resistant (CR) prostate cancer (CRPC). Little is known about the ARV-mediated transcription program in CRPC. We identified ARV-preferred binding sites (ARV-PBS) and unique transcriptome in CRPC cells. ARVs preferentially bind to enhancers located in nucleosome-depleted regions with the full AR-response element (AREfull), while full-length AR (ARFL)-PBS are enhancers resided in closed chromatin regions with the composite FOXA1-nnnn-AREhalf motif. ARV-PBS exclusively overlapped with AR binding sites in CR patients. ARV-driven genes were up-regulated in abiraterone-resistant patient specimens and promote CRPC growth. We uncover distinct genomic and epigenomic characteristics of ARV-PBS and a unique ARV-dependent transcriptional program that not only drives CR progression but could also offer new targets for therapy. Increasing evidence suggests a pivotal role of ARVs in the acquisition of anti-AR therapy resistance in CRPC. It has been shown previously that ARVs possess unique structural and functional features such as completely lacking or only containing an impaired ligand-binding domain but constitutively active. Our findings advance the understanding of ARVs by demonstrating that ARV-PBS exhibit distinctive DNA-binding motif, GC content, and nucleosome and epigenetic characteristics. We further unravel that ARV-PBS exclusively overlap with AR bindings identified from castration-resistant patients and ARV activity is significantly increased in abiraterone-resistant patients. Given that there is no drug available to target ARVs at present, identification of ARV-mediated unique downstream pathways opens new avenues for the development of effective therapeutics for CRPC.
 
Overall design ARVs preferred binding sites (ARV-PBS) were identified from regular AR ChIP-seq experiments after knocking down AR full length (ARFL) in 22Rv1 (R1881-). ARFL preferred binding sites (ARFL-PBS) were identified from regular AR ChIP-seq experiments after knocking down AR-V1, AR-V3, AR-V4 and AR-V7 in 22Rv1 (R1881+).
 
Contributor(s) Wang L, Ye Z, Lu J
Citation(s) 29309643
Submission date Apr 28, 2016
Last update date May 15, 2019
Contact name Zhenqing Ye
E-mail(s) iamyezhenqing@gmail.com
Organization name Mayo Clinic
Department Biomedical Statistics and Informatics
Street address 200 First St. SW
City Rochester
State/province MN
ZIP/Postal code 55905
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (25)
GSM2135700 H3K4me1_ChIPSeq
GSM2135701 H3K4me1_ChIPSeq_R1881
GSM2135702 H3K4me2_ChIPSeq
This SubSeries is part of SuperSeries:
GSE80743 Identification and characterization of androgen receptor splice variants preferred bindings that drive prostate cancer progression
Relations
BioProject PRJNA319901
SRA SRP074100

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE80742_RAW.tar 5.7 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap