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Series GSE65066 Query DataSets for GSE65066
Status Public on Feb 12, 2016
Title Activation of P-TEFb by enhancer RNAs associated with lethal prostate cancer [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Castration resistant prostate cancer (CRPC) is a lethal disease. Sustained aberrant activation of androgen receptor (AR) becomes a central mechanism that contributes to endocrine therapy resistance. Here, we demonstrate that AR-bound enhancer RNAs (AR-eRNAs), including eRNA of the KLK3 (or PSA) gene, are upregulated in human CRPC cells and patient tissues. By enhancing C-termine domain (CTD) serine-2 phosphorylation of RNA polymerase II (Pol II-Ser2p), PSA eRNA acts in cis to promote PSA mRNA transcription and in trans to induce mRNA expression of a large set of genes involved in androgen action, cell cycle progression and tumorgenesis. Accordingly, we demonstrate that PSA eRNA binds in vitro and in vivo to CYCLIN T1, a regulatory subunit of the positive transcription elongation factor b (P-TEFb) complex that mediates Pol II-Ser2p. To identify the PSA eRNA’s functions on the Pol II-Ser2p and CYCLINT1 in the CRPC C4-2 cells, we detected the Pol II-Ser2p and CYCLINT1 ChIP-seq with or without PSA eRNA knockdown in the C4-2 cells. Moreover, to rule out the AR binding changes and identify the AR binding sites around the new genes, we detected the AR ChIP-seq in LNCaP and C4-2 cells with or without the androgen.
Overall design Androgen receptor (AR) binding sites in human prostate cancer cell lines, LNCaP and C4-2, were studied using ChIP-seq. Pol II Ser-2p and CYCLINT1 binding sites in human prostate cancer cell lines C4-2 with or without PSA eRNA knockdown, were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
Contributor(s) Huang H, Zhao Y, Wang L
Citation(s) 27068475, 27221037
Submission date Jan 16, 2015
Last update date Mar 27, 2020
Contact name LIGUO WANG
Organization name Mayo Clinic
Department Division of Computational Biology
Street address 200 1st St SW
City Rochester
State/province MN
ZIP/Postal code 55905
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (18)
GSM1586658 AR_C42_EtOH_rep2
GSM1586659 AR_C42_EtOH_rep3
GSM1586660 AR_C42_Mib_rep2
This SubSeries is part of SuperSeries:
GSE55032 Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs
BioProject PRJNA272821
SRA SRP052553

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
GSE65066_RAW.tar 3.1 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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