ArticleProceedings of the National Academy of Sciences of the United States of America2015
Brd4 bridges the transcriptional regulators, Aire and P-TEFb, to promote elongation of peripheral-tissue antigen transcripts in thymic stromal cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 62 citations in OpenAlex.
- The CTNNB1-TRIM28 complex governs hormone-induced RNA polymerase II dynamics in kidney epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Systematic and proactive evaluation of AIRE missense variant effects.American journal of human genetics · 2026Article
- Multimerizing transcription factors FOXP3 and AIRE as chromatin architectural regulators.Nature immunology · 2026Review
- AIRE transcriptional condensates in central tolerance: a multiscale mechanistic perspective.Frontiers in immunology · 2026Review
- Systematic and proactive evaluation of AIRE missense variant effects.bioRxiv : the preprint server for biology · 2025Article
- Article
- Role of PRC2 in the stochastic expression of Aire target genes and development of mimetic cells in the thymus.The Journal of experimental medicine · 2025Article
- Thymic Interferons: A Little Goes a Long Way.Immunological reviews · 2025Review
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- Transcript splicing optimizes the thymic self-antigen repertoire to suppress autoimmunity.The Journal of clinical investigation · 2024Article
- Thymic Mimetic Cells: Ontogeny as Immunology.Annual review of cell and developmental biology · 2024Review
- Aire in Autoimmunity.Annual review of immunology · 2024Review
- FEZF2 and AIRE1: An Evolutionary Trade-off in the Elimination of Auto-reactive T Cells in the Thymus.Journal of molecular evolution · 2024Article
- A Germinal Center Checkpoint of AIRE in B Cells Limits Antibody Diversification.bioRxiv : the preprint server for biology · 2024Article
- Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis.Frontiers in immunology · 2024Review
- Novel Insights into the Autoimmunity from the Genetic Approach of the Human Disease.Advances in experimental medicine and biology · 2024Article
- Hnf4 activates mimetic-cell enhancers to recapitulate gut and liver development within the thymus.The Journal of experimental medicine · 2023Article
- Revisiting Aire and tissue-restricted antigens at single-cell resolution.Frontiers in immunology · 2023Review
- Thymic self-antigen expression for immune tolerance and surveillance.Inflammation and regeneration · 2022Review
- Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Aire controls immunologic tolerance by inducing a battery of thymic transcripts encoding proteins characteristic of peripheral tissues. Its unusually broad effect is achieved by releasing RNA polymerase II paused just downstream of transcriptional start sites. We explored Aire's collaboration with the bromodomain-containing protein, Brd4, uncovering an astonishing correspondence between those genes induced by Aire and those inhibited by a small-molecule bromodomain blocker. Aire:Brd4 binding depended on an orchestrated series of posttranslational modifications within Aire's caspase activation and recruitment domain. This interaction attracted P-TEFb, thereby mobilizing downstream transcriptional elongation and splicing machineries. Aire:Brd4 association was critical for tolerance induction, and its disruption could account for certain point mutations that provoke human autoimmune disease. Our findings evoke the possibility of unanticipated immunologic mechanisms subtending the potent antitumor effects of bromodomain blockers.
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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.