ArticleGenome biology2017
Regulatory landscape fusion in rhabdomyosarcoma through interactions between the PAX3 promoter and FOXO1 regulatory elements.
Article in Genome biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- PAX3: A Driver of Normal Development and Disease.Biomolecules · 2026Review
- CAR-T cell immunotherapy in rhabdomyosarcoma.Journal of translational medicine · 2026Review
- Epigenetic Regulation of Higher-Order Chromatin Structure (HOCS) and Its Implication in Human Diseases.Cancers · 2026Review
- FusOn-pLM: a fusion oncoprotein-specific language model via adjusted rate masking.Nature communications · 2025Article
- The Capicua C1 Domain Is Required for Full Activity of the CIC::DUX4 Fusion Oncoprotein.Cancer research communications · 2024Article
- ThebioRxiv : the preprint server for biology · 2024Article
- Enhancer-promoter specificity in gene transcription: molecular mechanisms and disease associations.Experimental & molecular medicine · 2024Review
- Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma.Frontiers in cell and developmental biology · 2024Review
- CRISPR-Cas9-Mediated Bioluminescent Tagging of Endogenous Proteins by Fluorescent Protein-Assisted Cell Sorting.Methods in molecular biology (Clifton, N.J.) · 2024Article
- PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors.Nature communications · 2023Article
- The 3D chromatin landscape of rhabdomyosarcoma.NAR cancer · 2023Article
- Differentiation-dependent chromosomal organization changes in normal myogenic cells are absent in rhabdomyosarcoma cells.bioRxiv : the preprint server for biology · 2023Article
- Differentiation-dependent chromosomal organization changes in normal myogenic cells are absent in rhabdomyosarcoma cells.Frontiers in cell and developmental biology · 2023Article
- The importance of considering regulatory domains in genome-wide analyses - the nearest gene is often wrong!Biology open · 2022Review
- Topologically Associating Domains and Regulatory Landscapes in Development, Evolution and Disease.Frontiers in cell and developmental biology · 2021Review
- Chromosome structural variation in tumorigenesis: mechanisms of formation and carcinogenesis.Epigenetics & chromatin · 2020Review
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- A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary.Molecular cell · 2020Article
- Chromatin Landscape During Skeletal Muscle Differentiation.Frontiers in genetics · 2020Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe organisation of vertebrate genomes into topologically associating domains (TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ectopic contacts.
resultsWe show that interactions within the PAX3 and FOXO1 domains are restricted to their respective TADs in normal conditions, while in a patient-derived alveolar rhabdomyosarcoma cell line, harbouring the diagnostic t(2;13)(q35;q14) translocation that brings together the PAX3 and FOXO1 genes, the PAX3 promoter interacts ectopically with FOXO1 sequences. Using a combination of 4C-seq datasets, we have modelled the three-dimensional organisation of the fused landscape in alveolar rhabdomyosarcoma.
conclusionsThe chromosomal translocation that leads to alveolar rhabdomyosarcoma development generates a novel TAD that is likely to favour ectopic PAX3:FOXO1 oncogene activation in non-PAX3 territories. Rhabdomyosarcomas may therefore arise from cells which do not normally express PAX3. The borders of this novel TAD correspond to the original 5'- and 3'- borders of the PAX3 and FOXO1 TADs, respectively, suggesting that TAD organisation precedes the formation of regulatory long-range interactions. Our results demonstrate that, upon translocation, novel regulatory landscapes are formed allowing new intra-TAD interactions between the original loci involved.
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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 OpenQuestion graph.