ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Tcra enhancer activation by inducible transcription factors downstream of pre-TCR signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Lineage- and stage-specific activity of antigen receptor gene enhancers during lymphocyte development.Frontiers in epigenetics and epigenomics · 2024Review
- E protein binding at theFrontiers in immunology · 2023Article
- Interleukin-7 receptor signaling is crucial for enhancer-dependent TCRδ germline transcription mediated through STAT5 recruitment.Frontiers in immunology · 2022Article
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function.International journal of molecular sciences · 2020Review
- A critical regulator of Bcl2 revealed by systematic transcript discovery of lncRNAs associated with T-cell differentiation.Scientific reports · 2019Article
- T-cell receptor α enhancer is inactivated in αβ T lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection.Nature immunology · 2015Article
- Recent insights into the transcriptional control of the Tcra/Tcrd locus by distant enhancers during the development of T-lymphocytes.Transcription · 2015Review
- Protein-DNA binding: complexities and multi-protein codes.Nucleic acids research · 2014Review
- Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent chromatin hub.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The Tcra enhancer (Eα) is essential for pre-TCR-mediated activation of germline transcription and V(D)J recombination. Eα is considered an archetypical enhanceosome that acts through the functional synergy and cooperative binding of multiple transcription factors. Based on dimethylsulfate genomic footprinting experiments, there has been a long-standing paradox regarding Eα activation in the absence of differences in enhancer occupancy. Our data provide the molecular mechanism of Eα activation and an explanation of this paradox. We found that germline transcriptional activation of Tcra is dependent on constant phospholipase Cγ, as well as calcineurin- and MAPK/ERK-mediated signaling, indicating that inducible transcription factors are crucially involved. NFAT, AP-1, and early growth response factor 1, together with CREB-binding protein/p300 coactivators, bind to Eα as part of an active enhanceosome assembled during pre-TCR signaling. We favor a scenario in which the binding of lymphoid-restricted and constitutive transcription factors to Eα prior to its activation forms a regulatory scaffold to recruit factors induced by pre-TCR signaling. Thus, the combinatorial assembly of tissue- and signal-specific transcription factors dictates the Eα function. This mechanism for enhancer activation may represent a general paradigm in tissue-restricted and stimulus-responsive gene regulation.
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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.