ArticlePLoS genetics2022
Divergent transcriptional and transforming properties of PAX3-FOXO1 and PAX7-FOXO1 paralogs.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting fusion proteins in solid tumors: from oncogenic mechanisms to clinical interventions.Acta pharmacologica Sinica · 2026Review
- Modeling of Capicua Family Fusion Oncoprotein-Driven Cancers Reveals Gene-Specific Functionality.Molecular cancer research : MCR · 2026Article
- A Pax7::Foxo1 conditional mouse strain.Skeletal muscle · 2026Article
- Comparative modes of chromatin engagement by PAX::FOXO1 fusions in rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2026Article
- Dual transcriptional activities of PAX3 and PAX7 spatially encode spinal cell fates through distinct gene networks.PLoS biology · 2025Article
- Large-scale discovery of chromatin dysregulation induced by oncofusions and other protein-coding variants.Nature biotechnology · 2025Article
- Article
- The Role of PAX7 in Breast Cancer Prognosis and Its Mechanistic Involvement in the Wnt/β-Catenin Pathway.Journal of cellular and molecular medicine · 2025Article
- Untangling the Role of MYC in Sarcomas and Its Potential as a Promising Therapeutic Target.International journal of molecular sciences · 2025Review
- Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS.Cancer medicine · 2025Article
- Fusion oncogenes in rhabdomyosarcoma: model systems, mechanisms of tumorigenesis, and therapeutic implications.Frontiers in oncology · 2025Review
- Cut&tag: a powerful epigenetic tool for chromatin profiling.Epigenetics · 2024Review
- Biological and therapeutic insights from animal modeling of fusion-driven pediatric soft tissue sarcomas.Disease models & mechanisms · 2024Review
- Epigenetic determinants of fusion-driven sarcomas: paradigms and challenges.Frontiers in cell and developmental biology · 2024Article
- PROTAC-Based Protein Degradation as a Promising Strategy for Targeted Therapy in Sarcomas.International journal of molecular sciences · 2023Review
- A perfusion-based three-dimensional cell culture system to model alveolar rhabdomyosarcoma pathological features.Scientific reports · 2023Article
- Targeting the Hedgehog Pathway in Rhabdomyosarcoma.Cancers · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hallmarks of the alveolar subclass of rhabdomyosarcoma are chromosomal translocations that generate chimeric PAX3-FOXO1 or PAX7-FOXO1 transcription factors. Overexpression of either PAX-FOXO1s results in related cell transformation in animal models. Yet, in patients the two structural genetic aberrations they derived from are associated with distinct pathological manifestations. To assess the mechanisms underlying these differences, we generated isogenic fibroblast lines expressing either PAX-FOXO1 paralog. Mapping of their genomic recruitment using CUT&Tag revealed that the two chimeric proteins have distinct DNA binding preferences. In addition, PAX7-FOXO1 binding results in greater recruitment of the H3K27ac activation mark than PAX3-FOXO1 binding and is accompanied by greater transcriptional activation of neighbouring genes. These effects are associated with a PAX-FOXO1-specific alteration in the expression of genes regulating cell shape and the cell cycle. Consistently, PAX3-FOXO1 accentuates fibroblast cellular traits associated with contractility and surface adhesion and limits entry into S phase. In contrast, PAX7-FOXO1 drives cells to adopt an amoeboid shape, reduces entry into M phase, and causes increased DNA damage. Altogether, our results argue that the diversity of rhabdomyosarcoma manifestation arises, in part, from the divergence between the genomic occupancy and transcriptional activity of PAX3-FOXO1 and PAX7-FOXO1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.