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Series GSE64656 Query DataSets for GSE64656
Status Public on Aug 01, 2015
Title Antagonistic interaction between androgen signaling and vitamin D signaling in prostate cancer [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Vitamin D induces anti-proliferative and differentiating effects in prostate cancer. Thus calcitriol, the hormonally active form of Vitamin D, and its analogs have been extensively studied in prostate cancer cells. Yet despite its importance, relatively little is known about the genome-scale mechanisms by which Vitamin D, through its cognate nuclear vitamin D receptor (VDR), exerts its regulatory functions at the genomic level. In this study, we defined VDR transcriptional networks in the LNCaP prostate cancer cell line by mapping the genomic binding sites of VDR and by identifying differentially expressed genes upon calcitriol treatment. We found that VDR and androgen receptor (AR) antagonistically regulate a subset of cell cycle-related genes that are over-expressed in prostate cancer tumors. The expression balance of these genes is partially regulated through the competition dynamics between AR and VDR binding to shared cis-regulatory elements. On such shared elements, we found that FOXA1 mediates this competition by serving as a pioneering factor for both AR and VDR binding. We also found significant enrichment of AR-, VDR-, and AR/VDR overlapping binding sites in prostate cancer-associated single-nucleotide polymorphism (SNP) intervals identified from genome-wide association studies (GWAS), providing genetic evidence to link AR, VDR and their crosstalk to prostate cancer susceptibilities. In particular, we found that in a cis-regulatory element of the RFX6 gene implicated in prostate cancer progression, an allelic variant increases prostate cancer risk by switching the antagonism between AR and VDR into a synergistic interaction.
 
Overall design Examination of AR, VDR, and FOXA1 binding in LNCaP cells, in biological replicates
 
Contributor(s) Liu Y, White KP
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Submission date Jan 05, 2015
Last update date May 15, 2019
Contact name Yuwen Liu
E-mail(s) yuwenliu@uchicago.edu
Phone 3128232822
Organization name University of Chicago
Department Human Genetics
Lab Kevin White's lab
Street address 900 East 57th Street. KCDB building. Room 10250
City Chicago
State/province IL
ZIP/Postal code 60637
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (6)
GSM1576447 AR LNCaP ChIP-Seq
GSM1576448 AR LNCaP Input
GSM1576449 VDR LNCaP ChIP-Seq
This SubSeries is part of SuperSeries:
GSE64657 Antagonistic interaction between androgen signaling and vitamin D signaling in prostate cancer
Relations
BioProject PRJNA271583
SRA SRP051692

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
GSE64656_RAW.tar 690.0 Kb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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