Dataset Information

Hepatic transcriptome analysis after acute and chronic glucocorticoid exposure combined with androgen receptor antagonism.

ABSTRACT: Hepatic transcriptome analysis after acute and chronic glucocorticoid exposure combined with androgen receptor antagonism.

PROVIDER: PRJNA748276 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR15197651.fastq.gz	Fastqsanger.gz
	SRR15197652.fastq.gz	Fastqsanger.gz
	SRR15197653.fastq.gz	Fastqsanger.gz
	SRR15197654.fastq.gz	Fastqsanger.gz
	SRR15197655.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 42

Similar Datasets

Project description:The androgen receptor plays a critical role throughout the progression of prostate cancer and is an important drug target for this disease. While chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq) is becoming an essential tool in studying transcription and chromatin modification factors, it has rarely been employed in the context of drug discovery. Here we report the first publicly available genome-wide and dose-dependent inhibition landscape of AR binding by drug-like small molecules including correlation with binding strength using ChIP-Seq. Integration of sequence analysis, transcriptome profiling, cell viability assays and in vivo tumor inhibition studies enabled us to establish a direct cistrome-activity relationship for two novel potent AR antagonists. By selectively occupying the strongest binding sites, AR signaling remains active even when low androgen levels are low, a scenario characteristic of first-line androgen ablation therapy. Coupled cistrome and transcriptome profiling upon small molecule antagonism led to the identification of not only key direct downstream effectors of AR but also their mode of regulation: unbiased pathway mapping revealed that AR is a key modulator of steroid metabolism by forming a tightly controlled feedback loop with other nuclear receptor family members. Furthermore, we found AR has an extensive role in negative gene regulation and estrogen (related) receptor likely mediates its function as a transcriptional repressor. In conclusion, our study provides a global and dynamic view of ARM-bM-^@M-^Ys regulatory program upon antagonism, which may serve as a molecular basis for deciphering and developing AR therapeutics. GSM814034-GSM814044: Compartative study of the mRNA profiles of VCaP cells treated with small molecule inhibitor of AR and those treated with AR-siRNA GSM817346-GSM817354: Comparative study of AR binding in VCaP cells (1) in the presence and absence of the synthetic AR agonist metribolone (R1881) and (2) in the presence of R1881 and small molecule inhibitors of AR

Dataset Information

Hepatic transcriptome analysis after acute and chronic glucocorticoid exposure combined with androgen receptor antagonism.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets