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Series GSE117430 Query DataSets for GSE117430
Status Public on Jul 18, 2019
Title CHD1 functions as a prostate-specific tumor suppressor by modulating nuclear receptor specificity towards distinct transcriptional programs [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Deregulation of chromatin architecture is emerging as a critical feature of carcinogenesis, and genomic alterations in nucleosome remodelers are common in human cancer. Recurrent deletion of the chromatin remodeler CHD1 is among the most common alterations in prostate cancer, but its role as a tumor suppressor and the reasons for the tissue-specific nature of CHD1 deletion remain undefined. Here, we show that deletion of CHD1 drives prostate tumorigenesis and fundamentally reprograms the transcriptional program of the androgen receptor (AR), diverting AR towards an oncogenic transcriptional program and away from a growth suppressive transcriptome. Conditional deletion of Chd1 in mouse prostate resulted in prostate neoplasia in vivo, confirming CHD1 as a tumor suppressor in prostate tissue. In prostate cells, the interactome of chromatin-bound CHD1 was enriched for factors that regulate nuclear receptor function, and interrogation of the CHD1 cistrome revealed promoter-independent enrichment of CHD1 at sites specifically occupied by AR and its associated transcriptional regulators. Deletion of CHD1 resulted in a dramatic redistribution of AR across the genome, localizing AR to sites enriched for HOXB13, and depleting AR at AR-halfsite motifs, consistent with the AR cistrome and epigenetic marks in human prostate cancer samples. Furthermore, the CHD1 null AR cistrome was associated with a unique AR transcriptional signature, enriched for pro-oncogenic pathways and depleted for processe consistent with normal prostatic function. Collectively, these data implicate CHD1 as a prostate-specific tumor suppressor which constrains the oncogenic functions of AR though maintenance of a normal AR transcriptional program.
 
Overall design LNCaP cells were initally assessed for genomic distribution of AR, CHD1, H3K4me3, H3K27me3, and cMYC under androgren proficient conditions using ChiP Sequencing. Each condtion/IP was conducted in biological duplicate and analyzed for tag enrichment as compared to input controls. The AR cistrome was also analyzed in the presence or absence of CHD1 in cells expressing with a scrambled (sgCtrl) or CHD1 targeting (sgCHD1) sgRNA. Tag enrichment was assessed for each biological replicate using sequneced input samples from each cell line as a control.
 
Contributor(s) Augello M, Barbieri CE
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Submission date Jul 20, 2018
Last update date Jul 18, 2019
Contact name Deli Liu
E-mail(s) del2017@med.cornell.edu
Organization name Weill Cornell Medicine
Street address 1300 York Ave
City New York
State/province New York
ZIP/Postal code 10021
Country USA
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (16)
GSM3294587 AR_2
GSM3294588 AR_3
GSM3294589 CHD1_2
This SubSeries is part of SuperSeries:
GSE117431 Loss of CHD1 facilitates oncogenic hijacking of AR during cancer progression
Relations
BioProject PRJNA482104
SRA SRP154551

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
GSE117430_AR_peaks.bed.gz 104.9 Kb (ftp)(http) BED
GSE117430_CHD1_peaks.bed.gz 225.4 Kb (ftp)(http) BED
GSE117430_H3K27me3_peaks.bed.gz 391.1 Kb (ftp)(http) BED
GSE117430_H3K4me3_peaks.bed.gz 233.2 Kb (ftp)(http) BED
GSE117430_cMYC_peaks.bed.gz 124.3 Kb (ftp)(http) BED
GSE117430_sgCHD1_AR_1_peaks.bed.gz 405.1 Kb (ftp)(http) BED
GSE117430_sgCHD1_AR_2_peaks.bed.gz 892.5 Kb (ftp)(http) BED
GSE117430_sgCTRL_AR_1_peaks.bed.gz 554.1 Kb (ftp)(http) BED
GSE117430_sgCTRL_AR_2_peaks.bed.gz 614.3 Kb (ftp)(http) BED
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Processed data are available on Series record

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