ArticleMolecular and cellular biology2012
Unmodified histone H3K4 and DNA-dependent protein kinase recruit autoimmune regulator to target genes.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Systematic and proactive evaluation of AIRE missense variant effects.American journal of human genetics · 2026Article
- 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
- A novel heterozygous pathogenicJournal of human immunity · 2025Article
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- Novel Insights into the Autoimmunity from the Genetic Approach of the Human Disease.Advances in experimental medicine and biology · 2024Article
- Thymic self-antigen expression for immune tolerance and surveillance.Inflammation and regeneration · 2022Review
- Aire and Fezf2, two regulators in medullary thymic epithelial cells, control autoimmune diseases by regulating TSAs: Partner or complementer?Frontiers in immunology · 2022Review
- Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus.Frontiers in pharmacology · 2021Review
- The Autoimmune Regulator (Aire) transactivates HLA-G gene expression in thymic epithelial cells.Immunology · 2019Article
- Bromodomain-containing protein 4-independent transcriptional activation by autoimmune regulator (AIRE) and NF-κB.The Journal of biological chemistry · 2018Article
- Twenty Years of AIRE.Frontiers in immunology · 2018Review
- Update on Aire and thymic negative selection.Immunology · 2018Review
- DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes.The Journal of biological chemistry · 2017Article
- FBXO3 Protein Promotes Ubiquitylation and Transcriptional Activity of AIRE (Autoimmune Regulator).The Journal of biological chemistry · 2016Article
- Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells.The Journal of biological chemistry · 2016Article
- AIRE expands: new roles in immune tolerance and beyond.Nature reviews. Immunology · 2016Review
- Brd4 bridges the transcriptional regulators, Aire and P-TEFb, to promote elongation of peripheral-tissue antigen transcripts in thymic stromal cells.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance.Nature immunology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Autoimmune regulator (AIRE) directs the expression of otherwise tissue-restricted antigens (TRAs) in medullary thymic epithelial cells, allowing their presentation to developing T cells, which leads to central tolerance. We addressed the conundrum of how AIRE is recruited to these otherwise silent genes in cells. Our studies confirmed that interactions between AIRE and the unmodified histone H3K4 (H3K4me0) are important for targeting AIRE to the mouse insulin promoter in chromatin. By replacing its H3K4me0-binding module with one that binds to the methylated H3K4me3, we redirected the mutant AIRE.ING protein to an actively transcribed gene. Nevertheless, the mutant AIRE D297A protein, which could not bind to H3K4me0, still activated the human insulin promoter on an episomal plasmid target. This targeting was due to DNA-dependent protein kinase (DNA-PK). Thus, in cells that lacked the catalytic subunit of DNA-PK (DNA-PKcs), the assembly and activity of AIRE on DNA, whether in chromatin or on episomal plasmids, was abrogated. However, by the heterologous tethering of AIRE to DNA, we could restore its activity on a plasmid target in DNA-PKcs-negative cells. Importantly, mutations in the putative DNA-binding residues in its SAND domain had no effect on the transcriptional effects of AIRE. Thus, AIRE is recruited to TRA genes in chromatin via cooperative interactions with H3K4me0 and DNA-PK.
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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.