ArticleThe EMBO journal2013
Epigenetic Thpok silencing limits the time window to choose CD4(+) helper-lineage fate in the thymus.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- ZBTB7B modulates the androgen receptor as an upstream regulator via colocalization and direct binding in LNCaP prostate cancer cells.Translational cancer research · 2025Article
- The histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development.The Journal of experimental medicine · 2021Article
- Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4Nature immunology · 2021Article
- ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells.Frontiers in immunology · 2021Review
- Control of Intra-Thymic αβ T Cell Selection and Maturation by H3K27 Methylation and Demethylation.Frontiers in immunology · 2019Review
- Runx-dependent and silencer-independent repression of a maturation enhancer in the Cd4 gene.Nature communications · 2018Article
- Tle corepressors are differentially partitioned to instruct CD8The Journal of experimental medicine · 2018Article
- IL-36γ signaling controls the induced regulatory T cell-Th9 cell balance via NFκB activation and STAT transcription factors.Mucosal immunology · 2017Article
- Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes.Nature communications · 2017Article
- Distinct requirement of Runx complexes for TCRβ enhancer activation at distinct developmental stages.Scientific reports · 2017Article
- Heritable Gene Regulation in the CD4:CD8 T Cell Lineage Choice.Frontiers in immunology · 2017Review
- Pleiotropic Functions of H3K27Me3 Demethylases in Immune Cell Differentiation.Trends in immunology · 2016Review
- Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation.Nature communications · 2015Article
- Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Stage-specific epigenetic gene silencing during thymocyte lineage commitment.F1000prime reports · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4(+) helper and CD8(+) cytotoxic T cells differentiate from common precursors in the thymus after T-cell receptor (TCR)-mediated selection. Commitment to the helper lineage depends on persistent TCR signals and expression of the ThPOK transcription factor, whereas a ThPOK cis-regulatory element, ThPOK silencer, represses Thpok gene expression during commitment to the cytotoxic lineage. Here, we show that silencer-mediated alterations of chromatin structures in cytotoxic-lineage thymocytes establish a repressive state that is epigenetically inherited in peripheral CD8(+) T cells even after removal of the silencer. When silencer activity is enhanced in helper-lineage cells, by increasing its copy number, a similar heritable Thpok silencing occurs. Epigenetic locking of the Thpok locus may therefore be an independent event from commitment to the cytotoxic lineage. These findings imply that long-lasting TCR signals are needed to establish stable Thpok expression activity to commit to helper T-cell fate and that full commitment to the helper lineage requires persistent reversal of silencer activity during a particular time window.
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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.