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CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (4C-Seq)

ABSTRACT: CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (4C-Seq)

PROVIDER: PRJNA1153602 | ENA |

REPOSITORIES: ENA

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CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (4C-Seq)

Project description:Amplification of the androgen receptor (AR) locus is the most frequent alteration in metastatic treatment resistant prostate cancer. Recently it was discovered that an enhancer of the AR is co-amplified with the AR gene body and contributes to increased AR transcription and resistance to androgen deprivation therapy. However, the mechanism of enhancer activation in advanced disease is unknown. Here, we used functional genetic screening to identify transcription factors that bind to the AR enhancer and are required for enhancer mediated AR transcription. We validated binding of the transcription factors, HOXB13, GATA2, and TFAP2C in patient derived xenografts and demonstrated differential effects on features associated with active chromatin state including H3K27ac, DNA accessibility, and enhancer-promoter interaction frequency. Interestingly, the AR enhancer belongs to a set of regulatory elements that requires HOXB13 to maintain FOXA1 binding, uncovering a novel role for HOXB13 in castration-resistant prostate cancer. This work provides a framework to functionally identify trans-acting factors required for activation of disease related noncoding regulatory elements.

2025-02-13 | GSE275926 | GEO

CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer

Project description:CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer

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CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer [ChIP-Seq]

Project description:CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer [ChIP-Seq]

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CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (RNA-Seq)

Project description:CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (RNA-Seq)

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CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (ATAC-Seq)

Project description:CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (ATAC-Seq)

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CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer [ChIP-Seq]

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CRISPR screening identifies regulators of enhancer mediated androgen receptor transcription in advanced prostate cancer (ATAC-Seq)

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Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists

Project description:Pathways modulating glucose homeostasis independently of insulin would open new avenues to combat insulin resistance and diabetes. Here, we report the establishment, characterization and use of a vertebrate 'insulin-free' model to identify insulin-independent modulators of glucose metabolism. insulin knockout zebrafish recapitulate core characteristics of diabetes and survive only up to larval stages. Utilizing a highly efficient endoderm transplant technique, we generated viable chimeric adults that provide the large numbers of insulin mutant larvae required for our screening platform. Using glucose as a disease-relevant readout, we screened 2233 molecules and identified 3 that consistently reduced glucose levels in insulin mutants. Most significantly, we uncovered an insulin-independent beneficial role for androgen receptor antagonism in hyperglycemia, mostly by reducing fasting glucose levels. Our study proposes therapeutic roles for androgen signaling in diabetes and, more broadly, offers a novel in vivo model for rapid screening and decoupling of insulin-dependent and -independent mechanisms.

2018-12-13 | PXD012027 | Pride

The Wnt/β-catenin-signaling pathway is modulated by androgen ablation therapy for advanced clinical prostate cancer and contributes to androgen independent cell growth

Project description:Androgen ablation therapy (AAT) is standard treatment for locally-advanced/metastatic prostate cancer (PCa). Many patients develop castration-resistance (CRPCa) after ~2-3 years, with a poor prognosis. The molecular mechanisms underlying CRPCa progression are unclear. mRNA-Seq was performed on tumours from 7 patients with locally-advanced/metastatic PCa before and ~22 weeks after AAT initiation. Differentially regulated genes were identified in treatment pairs. Tumour biopsies from 7 patients were taken before and after AAT treatment

2013-10-07 | E-GEOD-48403 | biostudies-arrayexpress

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