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Chromatin relaxation is a feature of advanced prostate cancer

ABSTRACT: Chromatin relaxation is a feature of advanced prostate cancer

PROVIDER: PRJNA298678 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2645760.fastq.gz	Fastqsanger.gz
	SRR2645770.fastq.gz	Fastqsanger.gz
	SRR2645780.fastq.gz	Fastqsanger.gz
	SRR2645761.fastq.gz	Fastqsanger.gz
	SRR2645771.fastq.gz	Fastqsanger.gz

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Chromatin relaxation is a feature of advanced prostate cancer [expression]

Project description:Altered patterns of transcription factor (TF) binding are now accepted as a hallmark of many aggressive cancers including prostate and breast cancers1,2. This implies that underlying global changes in chromatin accessibility may drive cancer progression, as previously hypothesized3-5. In addition there are epigenetic readers such as bromodomain containing protein 4 (BRD4), which have been shown to associate with these TFs6-8 and also to contribute to aggressive cancers of many types8,9 including prostate cancer (PC)6,10. Here we show for the first time that formaldehyde-assisted isolation of regulatory elements followed by sequencing (FAIRE-seq) applied to human prostate tumors tissue can define castrate-resistant prostate cancer (CRPC) and can be used to inform the discovery of gene-level classifiers for therapy. In addition, we show that the androgen receptor (AR) overexpression alone is a primary driver for chromatin relaxation and that this effect can be reversed using bromodomain inhibitors. We also report that bromodomain-containing proteins (BRDs) are overexpressed in advanced CRPCs and that ATAD2 and BRD2 have prognostic value. In conclusion, this is the first study demonstrating a major impact of BRDs on chromatin accessibility in CRPC in patient samples. Consequently, targeting bromodomains provides a compelling rational for combination therapy in which BRD-mediated TF binding is enhanced or modified as cancer progresses. Expression profile of LNCaP and VCaP prostate cancer cell lines treated with synthetic androgen R1881 with or without concomitant treatment with the pan-BET bromodomain inhibitor JQ1.

2017-06-06 | GSE73930 | GEO

Chromatin relaxation is a feature of advanced prostate cancer [FAIRE-Seq]

Project description:Altered patterns of transcription factor (TF) binding are now accepted as a hallmark of many aggressive cancers including prostate and breast cancers1,2. This implies that underlying global changes in chromatin accessibility may drive cancer progression, as previously hypothesized3-5. In addition there are epigenetic readers such as bromodomain containing protein 4 (BRD4), which have been shown to associate with these TFs6-8 and also to contribute to aggressive cancers of many types8,9 including prostate cancer (PC)6,10. Here we show for the first time that formaldehyde-assisted isolation of regulatory elements followed by sequencing (FAIRE-seq) applied to human prostate tumors tissue can define castrate-resistant prostate cancer (CRPC) and can be used to inform the discovery of gene-level classifiers for therapy. In addition, we show that the androgen receptor (AR) overexpression alone is a primary driver for chromatin relaxation and that this effect can be reversed using bromodomain inhibitors. We also report that bromodomain-containing proteins (BRDs) are overexpressed in advanced CRPCs and that ATAD2 and BRD2 have prognostic value. In conclusion, this is the first study demonstrating a major impact of BRDs on chromatin accessibility in CRPC in patient samples. Consequently, targeting bromodomains provides a compelling rational for combination therapy in which BRD-mediated TF binding is enhanced or modified as cancer progresses. FAIRE-seq study for LNCaP and VCaP prostate cancer cell lines hormone starved or treated with R1881, and human prostate tissue samples from benign prostate hyperplasia (BPH), primary prostate cancer (PC), and castrate resistant prostate cancer (CRPC) patients.

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Chromatin relaxation is a feature of advanced prostate cancer

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Project description:Chromatin relaxation is a feature of advanced prostate cancer [expression]

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Project description:Chromatin relaxation is a feature of advanced prostate cancer [FAIRE-Seq]

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Epigenetic landscape of advanced prostate cancer

Project description:Prostate cancer is characterized as being histologically and molecularly heterogeneous. Additionally, epigenetic changes play an important role in regulating the progression of prostate cancer. However, epigenetic intraindividual heterogeneity is largely unknown in advanced prostate cancer. Hence, the epigenetic profiles of advanced prostate cancer, including autopsy cases, were investigated.

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