Proteomics

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Defining the interactome of CHD4 in fusion-positive rhabdomyosarcoma


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Alveolar Sac

DISEASE(S): Alveolar Rhabdomyosarcoma

SUBMITTER: Fabian Frommelt  

LAB HEAD: Beat W. Schäfer

PROVIDER: PXD015231 | Pride | 2020-08-11

REPOSITORIES: Pride

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Publications

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

Marques Joana G JG   Gryder Berkley E BE   Pavlovic Blaz B   Chung Yeonjoo Y   Ngo Quy A QA   Frommelt Fabian F   Gstaiger Matthias M   Song Young Y   Benischke Katharina K   Laubscher Dominik D   Wachtel Marco M   Khan Javed J   Schäfer Beat W BW  

eLife 20200803


The NuRD complex subunit CHD4 is essential for fusion-positive rhabdomyosarcoma (FP-RMS) survival, but the mechanisms underlying this dependency are not understood. Here, a NuRD-specific CRISPR screen demonstrates that FP-RMS is particularly sensitive to CHD4 amongst the NuRD members. Mechanistically, NuRD complex containing CHD4 localizes to super-enhancers where CHD4 generates a chromatin architecture permissive for the binding of the tumor driver and fusion protein PAX3-FOXO1, allowing downst  ...[more]

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