ArticleThe Journal of experimental medicine2020
Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 57 citations in OpenAlex.
- Trial
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- Upregulation of ALDH1 as an adaptive epigenetic response to anthracyclines in acute myeloid leukemia.HemaSphere · 2025Article
- A pooled CRISPR screen identifies the Tα2 enhancer element as a driver ofFrontiers in immunology · 2025Article
- Enhancers in T Cell development and malignant lesions.Cell death discovery · 2024Review
- HOXA9 versus HOXB9; particular focus on their controversial role in tumor pathogenesis.Journal of applied genetics · 2024Review
- Short tandem repeats are important contributors to silencer elements in T cells.Nucleic acids research · 2023Article
- From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia.Nature communications · 2023Article
- TAL1 activation in T-cell acute lymphoblastic leukemia: a novel oncogenic 3' neo-enhancer.Haematologica · 2023Article
- Dynamics of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes.Genome research · 2022Article
- Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers.Genome research · 2022Article
- Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes.International journal of molecular sciences · 2022Article
- Logic and lineage impacts on functional transcription factor deployment for T-cell fate commitment.Biophysical journal · 2021Review
- Deregulation of enhancer structure, function, and dynamics in acute lymphoblastic leukemia.Trends in immunology · 2021Review
- Adenylate kinase 2 expression and addiction in T-ALL.Blood advances · 2021Article
- Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status. Among these, the TCRA gene enhancer (Eα) is in an open and unmethylated chromatin structure well before activation. Integrative analyses revealed that the HOXA5-9 transcription factors repress the Eα enhancer at early stages of T cell differentiation, while their decommission is required for TCRA locus activation and enforced αβ T lineage differentiation. Remarkably, the HOXA-mediated repression of Eα is paralleled by the ectopic expression of homeodomain-related oncogenes in T cell acute lymphoblastic leukemia. These results highlight an analogous enhancer repression mechanism at play in normal and cancer conditions, but imposing distinct developmental constraints.
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Registered trials
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.