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CHD4 regulates super-enhancer accessibility in fusion-positive rhabdomyosarcoma and is essential for tumor growth

ABSTRACT: CHD4 regulates super-enhancer accessibility in fusion-positive rhabdomyosarcoma and is essential for tumor growth

PROVIDER: PRJNA588286 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10417468.fastq.gz	Fastqsanger.gz
	SRR10417469.fastq.gz	Fastqsanger.gz
	SRR10417470.fastq.gz	Fastqsanger.gz
	SRR10417471.fastq.gz	Fastqsanger.gz
	SRR10417472.fastq.gz	Fastqsanger.gz

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Similar Datasets

CHD4 regulates super-enhancer accessibility in fusion-positive rhabdomyosarcoma and is essential for tumor growth

Project description:ATP-dependent chromatin remodelers modulate gene expression by regulating genome accessibility and can contribute to tumorigenesis. In fusion-positive rhabdomyosarcoma (FP-RMS), we have previously identified the chromatin remodeler and NuRD subunit CHD4 as an essential gene for tumor survival. Here, we demonstrate that the FP-RMS vulnerability to CHD4 goes beyond its function as a NuRD member. Mechanistically, CHD4 interacts with BRD4 and co-localizes with the tumor driver and fusion protein PAX3-FOXO1 at super-enhancers where it generates a chromatin architecture permissive for the binding of the fusion protein. This allows the positioning of RNA polymerase 2 at promoters and the expression of the oncogenic program of PAX3-FOXO1. Additionally, analysis of genome-wide cancer dependency databases identifies CHD4 amongst the NuRD subunits as general novel cancer vulnerability. Our findings describe, for the first time, CHD4 as a regulator of super-enhancer-mediated gene expression and establish this chromatin remodeler as an unexpected broad tumor susceptibility.

2019-12-20 | GSE140115 | GEO

Defining the interactome of CHD4 in fusion-positive rhabdomyosarcoma

Project description:The goal of this study was to explore in detail how the chromatin remodeler and NuRD subunit CHD4 controls the oncogenic signature of the tumor driver and fusion protein PAX3-FOXO1 in fusion-positive rhabdomyosarcoma. To this aim, we defined the interactome of CHD4 by LC-MS, identified its location in the genome by ChIP-seq, assessed its influence on DNA accessibility by DNase I hypersensitivity assays, and determined its target genes by RNA-seq.

2020-08-11 | PXD015231 | Pride

NuRD subunit CHD4 regulates super-enhancer accessibility in Rhabdomyosarcoma and represents a general tumor dependency

2020-08-08 | GSE155861 | GEO

Expression Profiling of human Fusion-Positive and Fusion-Negative Rhabdomyosarcoma

Project description:Genome-wide gene expression in 33 fusion-positive and 25 fusion-negative rhabdomyosarcoma cases was studied using GeneChip Human Genome U133 Plus2 (Affymetrix) Fusion-positive versus fusion-negative rhabdomyosarcoma tumors

2016-06-01 | E-GEOD-66533 | biostudies-arrayexpress

Expression Profiling of human Fusion-Positive and Fusion-Negative Rhabdomyosarcoma

Project description:Genome-wide gene expression in 33 fusion-positive and 25 fusion-negative rhabdomyosarcoma cases was studied using GeneChip Human Genome U133 Plus2 (Affymetrix)

2016-06-01 | GSE66533 | GEO

Longitudinal biopsies of fusion-positive rhabdomyosarcoma orthotopic xenografts

Project description:Longitudinal biopsies of fusion-positive rhabdomyosarcoma orthotopic xenografts

| PRJNA1003123 | ENA

Fusion Negative Rhabdomyosarcoma Cell Lines

Project description:Fusion Negative Rhabdomyosarcoma Cell Lines

| PRJNA330685 | ENA

Expression data for analysis of genes affected by CHD4 in alveolar rhabdomyosarcoma cell line Rh4

Project description:CHD4 is an ATPase able to use the energy from ATP to shift or remove nucleosomes from specific sites in the chromatin, thereby affecting accessability of gene regulatory elements. It is part of the NuRD complex. The effect of CHD4 on global gene expression was evaluated in Rh4 alveolar rhabdomyosarcoma cells.

2015-09-29 | GSE73480 | GEO

NuRD subunit CHD4 regulates super-enhancer accessibility in Rhabdomyosarcoma and represents a general tumor dependency

Project description:NuRD subunit CHD4 regulates super-enhancer accessibility in Rhabdomyosarcoma and represents a general tumor dependency

| PRJNA655884 | ENA

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma

Project description:To date, there are no known prognostic markers identified in patients with fusion gene-negative rhabdomyosarcoma. This study validates the 5-gene (MG5) signature as a prognostic marker in patients with fusion negative intermediate-risk rhabdomyosarcoma clearly stratifying this otherwise clinically homogenous population of patients into two risk groups based on outcome. In addition, this analysis was performed using nCounter assay on paraffin embedded tissues and the results were concordant to previously published results using frozen tissues in a different patient cohort. Therefore, this work holds tremendous translational relevance as the MG5 signature can be reliably assessed in readily available paraffin embedded tissues of fusion gene-negative rhabdomyosarcoma patients in prospective clinical trials to stratify them into prognostic risk groups as well as to potentially tailor future therapy based on these risk groups.

2015-07-31 | E-MTAB-3580 | biostudies-arrayexpress

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