ArticleThe Journal of clinical investigation2016
Helicase CHD4 is an epigenetic coregulator of PAX3-FOXO1 in alveolar rhabdomyosarcoma.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Paediatric Therapeutic Development Workshop on rhabdomyosarcoma.British journal of cancer · 2026Review
- PAX3::FOXO1-Targeting PROTAC Induces Myogenic Differentiation of Fusion-Positive Rhabdomyosarcoma Cells.Cancers · 2026Article
- Molecular Targets in Alveolar Rhabdomyosarcoma: A Narrative Review of Progress and Pitfalls.International journal of molecular sciences · 2025Review
- DNA methylation patterns are influenced by Pax3::Foxo1 expression and developmental lineage in rhabdomyosarcoma tumours forming in genetically engineered mouse models.The Journal of pathology · 2025Article
- Review
- Review
- CRISPR-Cas9-Mediated Bioluminescent Tagging of Endogenous Proteins by Fluorescent Protein-Assisted Cell Sorting.Methods in molecular biology (Clifton, N.J.) · 2024Article
- PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution.Nature communications · 2023Article
- ZEB1 Is Regulated by K811 Acetylation to Promote Stability, NuRD Complex Interactions, EMT, and NSCLC Metastasis.Molecular cancer research : MCR · 2023Article
- Small Molecule Inhibitors as Therapeutic Agents Targeting Oncogenic Fusion Proteins: Current Status and Clinical.Molecules (Basel, Switzerland) · 2023Review
- Genomic and Epigenetic Changes Drive Aberrant Skeletal Muscle Differentiation in Rhabdomyosarcoma.Cancers · 2023Review
- The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer.Journal of translational medicine · 2023Article
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
- PAX3-FOXO1 coordinates enhancer architecture, eRNA transcription, and RNA polymerase pause release at select gene targets.Molecular cell · 2022Article
- Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma.Science translational medicine · 2022Article
- Divergent transcriptional and transforming properties of PAX3-FOXO1 and PAX7-FOXO1 paralogs.PLoS genetics · 2022Article
- The transcription factor PAX8 promotes angiogenesis in ovarian cancer through interaction with SOX17.Science signaling · 2022Article
- Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma.Frontiers in oncology · 2022Review
- Article
- Epigenetic regulator BMI1 promotes alveolar rhabdomyosarcoma proliferation and constitutes a novel therapeutic target.Molecular oncology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A vast number of cancer genes are transcription factors that drive tumorigenesis as oncogenic fusion proteins. Although the direct targeting of transcription factors remains challenging, therapies aimed at oncogenic fusion proteins are attractive as potential treatments for cancer. There is particular interest in targeting the oncogenic PAX3-FOXO1 fusion transcription factor, which induces alveolar rhabdomyosarcoma (aRMS), an aggressive cancer of skeletal muscle cells for which patient outcomes remain dismal. In this work, we have defined the interactome of PAX3-FOXO1 and screened 60 candidate interactors using siRNA-mediated depletion to identify candidates that affect fusion protein activity in aRMS cells. We report that chromodomain helicase DNA binding protein 4 (CHD4), an ATP-dependent chromatin remodeler, acts as crucial coregulator of PAX3-FOXO1 activity. CHD4 interacts with PAX3-FOXO1 via short DNA fragments. Together, they bind to regulatory regions of PAX3-FOXO1 target genes. Gene expression analysis suggested that CHD4 coregulatory activity is essential for a subset of PAX3-FOXO1 target genes. Depletion of CHD4 reduced cell viability of fusion-positive but not of fusion-negative RMS in vitro, which resembled loss of PAX3-FOXO1. It also caused specific regression of fusion-positive xenograft tumors in vivo. Therefore, this work identifies CHD4 as an epigenetic coregulator of PAX3-FOXO1 activity, providing rational evidence for CHD4 as a potential therapeutic target in aRMS.
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