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Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells (ChIP-seq)

ABSTRACT: Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells (ChIP-seq)

PROVIDER: PRJNA1106388 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28856469.fastq.gz	Fastqsanger.gz
	SRR28856470.fastq.gz	Fastqsanger.gz
	SRR28856471.fastq.gz	Fastqsanger.gz
	SRR28856472.fastq.gz	Fastqsanger.gz
	SRR28856473.fastq.gz	Fastqsanger.gz

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Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells

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Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells (scRNA-seq)

Project description:Steroid receptors are involved in a wide array of crosstalk mechanisms that regulate diverse biological processes, with significant implications in diseases, particularly in cancers. In prostate cancer, indirect crosstalk between androgen receptor (AR) and glucocorticoid receptor (GR) is well-documented, where GR replaces antiandrogen inactivated AR becoming the disease driver. However, the existence and impact of direct chromatin crosstalk between AR and GR in prostate cancer have remained elusive. Our genome-wide investigations reveal that AR activation significantly expands GR chromatin binding. Mechanistically, AR induces remodeling of closed chromatin sites, facilitating GR binding to normally inaccessible sites. Importantly, coactivation of AR and GR results in distinct transcriptional responses at both the population and single-cell levels. Intriguingly, genes and pathways affected by these transcriptional changes are generally associated with improved patient survival. Thus, the direct crosstalk between AR and GR yields markedly different outcomes from the known role of GR in circumventing AR blockade by antiandrogens.

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Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells (GRO-seq)

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FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells (mRNA)

Project description:We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate and mifepristone (RU486) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies. Expression profiling by microarray of LNCaP-1F5 cells treated with vehicle, 100 nM 5a-dihydrotestosterone (DHT), 100 nM dexamethasone (Dex), 1000 nM cyproterone acetate (CPA), 100 nM mifepristone (RU486) and combination of 100 nM DHT,100 nM Dex for 24 hours.

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