ArticleThe Journal of pathology2012
An integrated functional genomics approach identifies the regulatory network directed by brachyury (T) in chordoma.
Article in The Journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- Immune infiltration is associated with distinct transcriptional states and metabolic profiles in chordomas.iScience · 2026Article
- From Histology to Multi-Omics: Review of Chordoma Classification and Its Clinical Implications.Cells · 2026Review
- The TBXT rs2305089 SNP links the benign notochordal cell tumour and chordoma.The Journal of pathology · 2025Article
- Single-cell Transcriptomic Studies Unveil Potential Nodes of the Notochord Gene Regulatory Network.Integrative and comparative biology · 2024Review
- Chordoma cells possess bone-dissolving activity at the bone invasion front.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Cis-regulatory interfaces reveal the molecular mechanisms underlying the notochord gene regulatory network of Ciona.Nature communications · 2024Article
- Multimodal profiling of chordoma immunity reveals distinct immune contextures.Journal for immunotherapy of cancer · 2024Article
- Conserved enhancers control notochord expression of vertebrate Brachyury.Nature communications · 2023Article
- Virus-like particle-based delivery of Cas9/guide RNA ribonucleoprotein efficiently edits the brachyury gene and inhibits chordoma growth in vivo.Discover oncology · 2023Article
- Next-generation plasmids for transgenesis in zebrafish and beyond.Development (Cambridge, England) · 2023Article
- A correlation analysis of sacrococcygeal chordoma imaging and clinical characteristics with the prognostic factors.Frontiers in oncology · 2022Article
- Emerging target discovery and drug repurposing opportunities in chordoma.Frontiers in oncology · 2022Review
- Eomes function is conserved between zebrafish and mouse and controls left-right organiser progenitor gene expression via interlocking feedforward loops.Frontiers in cell and developmental biology · 2022Article
- Brachyury controlsDevelopment (Cambridge, England) · 2021Article
- Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death.Cancer research · 2020Article
- Transactivation of SOX5 by Brachyury promotes breast cancer bone metastasis.Carcinogenesis · 2020Article
- New Prospects for Molecular Targets for Chordomas.Neurosurgery clinics of North America · 2020Review
- [Chordoma: is there a molecular basis for diagnosis and treatment?]Der Pathologe · 2020Review
- Translational Windows in Chordoma: A Target Appraisal.Frontiers in neurology · 2020Review
- The Role of Transcriptional Factor Brachyury on Cell Cycle Regulation in Non-small Cell Lung Cancer.Frontiers in oncology · 2020Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Chordoma is a rare malignant tumour of bone, the molecular marker of which is the expression of the transcription factor, brachyury. Having recently demonstrated that silencing brachyury induces growth arrest in a chordoma cell line, we now seek to identify its downstream target genes. Here we use an integrated functional genomics approach involving shRNA-mediated brachyury knockdown, gene expression microarray, ChIP-seq experiments, and bioinformatics analysis to achieve this goal. We confirm that the T-box binding motif of human brachyury is identical to that found in mouse, Xenopus, and zebrafish development, and that brachyury acts primarily as an activator of transcription. Using human chordoma samples for validation purposes, we show that brachyury binds 99 direct targets and indirectly influences the expression of 64 other genes, thereby acting as a master regulator of an elaborate oncogenic transcriptional network encompassing diverse signalling pathways including components of the cell cycle, and extracellular matrix components. Given the wide repertoire of its active binding and the relative specific localization of brachyury to the tumour cells, we propose that an RNA interference-based gene therapy approach is a plausible therapeutic avenue worthy of investigation.
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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.