Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD003262
PROVIDER: PRJNA271256 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1735553.fastq.gz | Fastqsanger.gz | |||
| SRR1735554.fastq.gz | Fastqsanger.gz | |||
| SRR1735555.fastq.gz | Fastqsanger.gz | |||
| SRR1735556.fastq.gz | Fastqsanger.gz | |||
| SRR1735557.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 13 |
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Project description:Assembly of methylated LSD1 and CHD1 drives AR-dependent transcription and translocation
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Project description:Assembly of methylated LSD1 and CHD1 drives AR-dependent transcription and translocation [RNA-Seq]
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Project description:The aim of the study is to identify AR target gens in LNCaP cells 5 samples corresponding to LSD1 K114me2 or CHD1 genome-binding in DHT-treated and control LNCaP cells. 6 samples corresponding to LSD1 K114me2 or CHD1 genome-binding in LNCaP cells knocked-down for LSD1 or CHD1 and treated with DHT.
2015-12-07 | E-GEOD-64528 | biostudies-arrayexpress
Project description:LSD1 (also known as KDM1A) is a histone demethylase and a key regulator of gene expression in embryonic stem cells and cancer.1,2 LSD1 was initially identified as a transcriptional repressor via its demethylation of active histone H3 marks (di-methyl lysine 4 [2MK4]).1 In prostate cancer, specifically, LSD1 also co-localizes with the AR and demethylates repressive 2MK9 histone marks from androgen-responsive AR target genes, facilitating androgen-mediated induction of AR-regulated gene expression and androgen-induced proliferation in androgen-dependent cancers. We report here that the LSD1 protein is universally upregulated in human CRPC and promotes survival of CRPC cell lines. This effect is explained in part by LSD1-induced activation of cell cycle and embryonic stem cell gene setsâgene sets enriched in transcriptomal studies of lethal human tumors. Importantly, despite the fact that many of these genes are direct LSD1 targets, we did not observe histone methylation changes at the LSD1-bound regions, demonstrating non-canonical histone demethylation-independent mechanisms of gene regulation. This ChIP-seq dataset included H3K4me2 and H3K9me2 ChIP-seq data for siRNA target against LSD1 and non-targeting control, as well as SP2509 inhibition of LSD1 and mock treatment 4 conditions: siRNA against LSD1, siRNA against luciferase (non-targeting control); SP2509 inhibition of LSD1, mock treatment. There are 2 replicates per condition.
2016-06-30 | E-GEOD-77762 | biostudies-arrayexpress
Project description:Purpose: The goal of this study is to identify genome-wide changes in AR chromatin binding that occur in a human prostate cell line with knockdown of MAP3K7(TAK1) and CHD1, in the presence and absence of androgens. We utilize this cell line as a model of an aggressive prostate cancer subtype consisting of deletions of both MAP3K7 and CHD1 in human patients. ChIP-seq comparing AR chromatin binding in shControl, shMAP3K7(TAK1), shCHD1, and both (shMAP3K7/shCHD1) was used to identify AR cistrome changes resulting from loss of each of these genes. Abstract of associated study: Prostate cancer (PCa) genomic subtypes that stratify aggressive disease and inform treatment decisions at the primary stage are currently limited. Previously, we functionally validated an aggressive subtype present in 15% of PCa characterized by dual deletion of MAP3K7 and CHD1. Recent studies in the field have focused on deletion of CHD1 and its role in androgen receptor (AR) chromatin distribution and resistance to AR-targeted therapy, however, CHD1 is rarely lost without co-deletion of MAP3K7. Here we show that in the clinically relevant context of co-loss of MAP3K7 and CHD1 there are significant, collective changes to aspects of AR signaling. While CHD1 loss mainly impacts the expansion of the AR cistrome, loss of MAP3K7 drives increased AR target gene expression. PCa cell line models engineered to co-suppress MAP3K7 and CHD1 also demonstrated increased AR-v7 expression and resistance to the AR-targeting drug enzalutamide. Furthermore, we determined that low protein expression of both genes is significantly associated with biochemical recurrence (BCR) in a clinical cohort of radical prostatectomy specimens. Low MAP3K7 expression, however, was the strongest independent predictor for risk of BCR over all other tested clinicopathologic factors including CHD1 expression. Collectively, these findings illustrate the importance of MAP3K7 loss in a molecular subtype of PCa that poses challenges to conventional therapeutic approaches.
2021-04-12 | GSE168651 | GEO
Project description: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 processes 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.
2019-07-18 | GSE123333 | GEO
Project description: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.
2019-07-18 | GSE117430 | GEO
Project description: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.
2019-07-18 | GSE117429 | GEO
Project description:LSD1 (also known as KDM1A) is a histone demethylase and a key regulator of gene expression in embryonic stem cells and cancer. LSD1 was initially identified as a transcriptional repressor via its demethylation of active histone H3 marks (di-methyl lysine 4 [2MK4]). In prostate cancer, specifically, LSD1 also co-localizes with the AR and demethylates repressive 2MK9 histone marks from androgen-responsive AR target genes, facilitating androgen-mediated induction of AR-regulated gene expression and androgen-induced proliferation in androgen-dependent cancers. Recently, it was shown that treatment with high doses of androgens (e.g.10-fold higher doses than those required for induction of expression of androgen-activated genes such as PSA) recruits LSD1 and AR to an enhancer within the AR; this AR and LSD1 recruitment represses AR transcription. Thus, LSD1 appears to play a role in mediating both the proliferative and repressive phases of the biphasic androgen dose-response curve. For these reasons, we hypothesized that LSD1 might be important for maintenance of AR signalling in castration-resistant prostate cancer (CRPC) tumors. However, in this report, we describe a distinct role of LSD1 as a driver of proliferation and survival of prostate cancer cells, including CRPC cells, irrespective of androgens or even AR expression. Specifically, LSD1 activates expression of cell cycle, mitosis, and embryonic stem cell maintenance pathways that are enriched in lethal prostate cancers - pathways not activated by androgens. Finally, we observe that treatment with a new LSD1 inhibitor potently and specifically suppresses LSD1 function and suppresses CRPC growth and survival in vitro and in vivo. Our data place LSD1 as a key driver of androgen-independent survival in lethal prostate cancers and demonstrate the potential of LSD1-directed therapies in the near-term. The enclosed files are from microarrays experiments after suppressing LSD1 with RNAi or stimulating cells with the androgen agonist dihydrotestosterone (DHT).
2016-06-30 | E-GEOD-61630 | biostudies-arrayexpress
Project description:Translocation of ETS transcription factors including ERG and ETV1 occur in half of all prostate cancers. LNCaP cells harbor an ETV1 translocation. We performed ChIP-Seq analysis to determine the role of ETV1 on AR binding. The localization of enhancers were determined by H3K4me1 ChIP-Seq. To determine ETV1 and H3K4me1 localization, logarithmically growing cells
2013-06-13 | E-GEOD-47120 | biostudies-arrayexpress