Dataset Information


Identification and characterization of androgen receptor splice variants preferred bindings that drive prostate cancer progression [ChIP-seq]

ABSTRACT: 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+).

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Zhenqing Ye  

PROVIDER: GSE80742 | GEO | 2018-03-07


altmetric image


Androgen receptor splice variants bind to constitutively open chromatin and promote abiraterone-resistant growth of prostate cancer.

He Yundong Y   Lu Ji J   Ye Zhenqing Z   Hao Siyuan S   Wang Liewei L   Kohli Manish M   Tindall Donald J DJ   Li Benyi B   Zhu Runzhi R   Wang Liguo L   Huang Haojie H  

Nucleic acids research 20180201 4

Androgen receptor (AR) splice variants (ARVs) are implicated in development of castration-resistant prostate cancer (CRPC). Upregulation of ARVs often correlates with persistent AR activity after androgen deprivation therapy (ADT). However, the genomic and epigenomic characteristics of ARV-dependent cistrome and the disease relevance of ARV-mediated transcriptome remain elusive. Through integrated chromatin immunoprecipitation coupled sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis,  ...[more]

Similar Datasets

| GSE80741 | GEO
2016-05-22 | E-GEOD-80256 | ArrayExpress
2016-05-22 | E-GEOD-80450 | ArrayExpress
| GSE80450 | GEO
| GSE80256 | GEO
| GSE55345 | GEO
2012-03-17 | E-GEOD-36549 | ArrayExpress
2015-03-02 | E-GEOD-60841 | ArrayExpress
2013-02-06 | E-GEOD-42232 | ArrayExpress
| GSE71334 | GEO