Similar Datasets
Project description:Genome wide occupany of CTCF, H3K27ac and AR
2020-04-27 | GSE121021 | GEO
Project description:In castration-resistant prostate cancer (CRPC), clinical response to androgen receptor (AR) antagonists is limited mainly due to AR-variants expression and restored AR signaling. The metabolite spermine is most abundant in prostate and it decreases as prostate cancer progresses, but its functions remain poorly understood. Here, we show spermine inhibits full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) signaling and suppresses CRPC cell proliferation by directly binding and inhibiting protein arginine methyltransferase PRMT1. Spermine reduces H4R3me2a modification at the AR locus and suppresses AR binding as well as H3K27ac modification levels at AR target genes. Spermine supplementation restrains CRPC growth in vivo. PRMT1 inhibition also suppresses AR-FL and AR-V7 signaling and reduces CRPC growth. Collectively, we demonstrate spermine as an anticancer metabolite by inhibiting PRMT1 to transcriptionally inhibit AR-FL and AR-V7 signaling in CRPC, and we indicate spermine and PRMT1 inhibition as powerful strategies overcoming limitations of current AR-based therapies in CRPC.
2023-10-11 | MTBLS8034 | MetaboLights
Project description:Prostate-specific membrane antigen (PSMA) has emerged as an important therapeutic target in metastatic castration-resistant prostate cancer (CRPC). However, not all patients respond to PSMA-targeted therapy, in part due to heterogeneity of tumor expression of the target PSMA. Furthermore, loss of PSMA expression develops in up to 15-20% of patients with CRPC, and the underlying mechanisms remain poorly defined. In this study,To investigate possible epigenetic regulation of PSMA in the context of HOXB13-independent PSMA-suppressed tumors, we performed ChIPseq to evaluate the activation mark Histone H3 Lysine 27 acetylation (H3K27ac) on our previously characterized organoids. Similar to AR-positive, PSMA-positive 22Rv1 cells, the AR-negative, PSMA-positive NEPC model WCM1262 demonstrated H3K27ac at the PSMA (FOLH1) gene promotor corresponding with high PSMA expression, whereas other PSMA-negative NEPC models demonstrated low H3K27ac.
2023-01-30 | GSE221613 | GEO
Project description:We performed transcriptional profiling and chromatin immunoprecipitation for the key oncogenic driver in prostate cancer, Androgen Receptor (AR) and FOXA1, H3K27ac, H3K27me3 and CTCF to chart the epigenomic landscape in four clonal metastatic tumors from a single prostate cancer patient whose clinical course was closely followed over 17 years. The vast majority (~80% ) of all AR binding sites were shared among all samples and found in normal prostate tissue and primary prostate cancers signifying core binding events within the prostate lineage. Remarkably, active (H3K27ac marked) metastatic sample-specific AR binding sites showed no differential transcriptional output, indicating a robustness of transcriptional programming across different metastases samples.
2021-03-11 | GSE151619 | GEO
Project description:We performed transcriptional profiling and chromatin immunoprecipitation for the key oncogenic driver in prostate cancer, Androgen Receptor (AR) and FOXA1, H3K27ac, H3K27me3 and CTCF to chart the epigenomic landscape in four clonal metastatic tumors from a single prostate cancer patient whose clinical course was closely followed over 17 years. The vast majority (~80% ) of all AR binding sites were shared among all samples and found in normal prostate tissue and primary prostate cancers signifying core binding events within the prostate lineage. Remarkably, active (H3K27ac marked) metastatic sample-specific AR binding sites showed no differential transcriptional output, indicating a robustness of transcriptional programming across different metastases samples.
2021-03-11 | GSE152230 | GEO
Project description:STAG2, a member of cohesin, is one of the most recurrently mutated genes in human cancer. Here, we investigated STAG2 function in the context of Ewing sarcoma. Using a CRISPR/Cas9 approach, we generated two STAG2 knock-out isogenic clones (A673_SA2m#1 and TC71_SA2m#2) derived from A673 and TC71 STAG2 wild type (WT) Ewing sarcoma cell line. A STAG2 rescue model (A673_SA2r) was generated by correcting the CRISPR mutation in the A673_SA2m#1 model. These STAG1/2 proficient and deficient models were profiled by CTCF HiChIP experiments. STAG2 isogenic models were also profiled by H3K27ac HiChIP experiments. Analyses of HiChIP data allowed to show that STAG2 promotes CTCF-anchored loop extrusion and cis-promoter and -enhancer interactions.
2021-04-29 | GSE133227 | GEO
Project description:We report the efficacy of androgen receptor inverse agonists (ARIAs) in altering androgen receptor (AR) transcriptional activity. Through RNA-sequencing studies in a panel of prostate cancer cell lines and patient derived xenograft models, we demonstrate ARIAs succcessfully inhibit androgen response gene sets. ChIP-seq and CUT&RUN studies demonstrate H3K27ac decreases at AR-target genes in response to treatment. AR and NCOR1/2 localizes at these regions of acetylation loss. HiChIP further revealed loss of 3D connectivity in reponse to ARIA treatment,
2023-06-25 | GSE205980 | GEO
Project description:Genome-wide association studies (GWAS) have revolutionized the field of cancer genetics, but the causal links between increased genetic risk and onset/progression of disease processes remain to be identified. Here we report the first step in such an endeavor for prostate cancer. We provide a comprehensive annotation of the 77 known risk loci, based upon highly correlated variants in biologically relevant chromatin annotations- we identified 727 such potentially functional SNPs. We also provide a detailed account of possible protein disruption, microRNA target sequence disruption and regulatory response element disruption of all correlated SNPs at r^2≥0.5. Greater than 88% of the 727 SNPs fall within putative enhancers, many of which alter critical residues in the response elements of transcription factors known to be involved in prostate biology. We define as risk enhancers those regions with enhancer chromatin biofeatures in prostate-derived cell lines with prostate-cancer correlated SNPs. To aid in the identification of these enhancers, we performed genomewide ChIP-seq for H3K27-acetylation, a mark of actively engaged enhancer regions, as well as the transcription factor TCF7L2. We analyzed in depth three variants in risk enhancers, two of which show significantly altered androgen sensitivity in LNCaP cells. This includes rs4907792, that is in linkage disequilibrium (r^2=0.91) with an eQTL for NUDT11 (on the X chromosome) in prostate tissue, and rs10486567, the index SNP in intron 3 of the JAZF1 gene on chromosome 7. Rs4907792 is within a critical residue of a strong consensus androgen response element that is interrupted in the protective allele, resulting in a 56% decrease in its androgen sensitivity, whereas rs10486567 affects both NKX3-1 and FOXA-AR motifs where the risk allele results in a 39% increase in basal activity and a 28% fold-increase in androgen stimulated enhancer activity. Identification of such enhancer variants and their potential target genes represents a preliminary step in connecting risk to disease process. ChIP-seq analysis of H3K27Ac in LNCaP charcoal-stripped serum, H3K27Ac in LNCaP charcoal-stripped serum +DHT, TCF7L2 in LNCaP
2014-01-28 | E-GEOD-51621 | biostudies-arrayexpress
Project description:To elucidate the AR-V7 role, we performed ChIP-seq on H3K4me1, H3K4me3, H3K27ac, and AR antibody recognizing the N-terminus of AR and AR splice variants (AR-Vs) using LNCaP and LNCaP95 cells. We showed 399 AR-V7 targeted regions in LNCaP95, most of the AR-V7 target regions could be commonly activated by hormone stimulated AR. However, 22 regions were identified as AR-V7 specific regions. In addition, we show here that AR-V7 can transcript in the ligand independent manner in LNCaP95, unlike LNCaP. We identified the AR-V7 target gene contributing to the CRPC progression.
2020-11-02 | GSE122922 | GEO
Project description:The spliced variant forms of androgen receptor (AR-Vs) have been identified recently in castration-resistant prostate cancer (CRPC) cell lines and clinical samples. Here we identified the cistrome and transcriptome landscape of AR-Vs in CRPC cell lines and determine the clinical significance of AR variants regulated gene.The AR variants binding sites can be identified in 22Rv1 cell line in the absence of androgen. Knocking down full-length AR (AR-FL) doesn't affect AR-Vs binding sites in genome-wide. A set of genes were identified to be regulated uniquely by AR-Vs, but not by AR-FL in androgen-depleted condition. Integrated analysis showed that some genes may be modulated by AR-Vs directly. Unsupervised clustering analysis demonstrated that AR variants gene signature can separate not only the benign and malignant prostate tissue, but also the localized prostate cancer and metastatic CRPC specimens. Some genes modulated uniquely by AR variants were also identified to correlate with the Gleason Pattern of prostate cancer and PSA failure. We conclude that AR spliced variants bind to DNA independent of full-length AR, and can modulate a unique set of genes which is not regulated by full-length AR in the absence of androgen. AR variants gene signature correlate with CRPC and prostate cnacer disease progress. Androgen receptor (AR) binding sites in human prostate cancer 22Rv1 cell lines were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
2014-09-10 | E-GEOD-58478 | biostudies-arrayexpress