ArticleThe Journal of biological chemistry2017
DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Thymic Interferons: A Little Goes a Long Way.Immunological reviews · 2025Review
- Weighted Gene Co-expression Network Analysis and Machine Learning Validation for Identifying Major Genes Related to Sjogren's Syndrome.Biochemical genetics · 2025Article
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- High-mobility group box 1 in acute kidney injury.Frontiers in pharmacology · 2025Review
- High-resolution transcriptional impact of AIRE: effects of pathogenic variants p.Arg257Ter, p.Cys311Tyr, and polygenic risk variant p.Arg471Cys.Frontiers in immunology · 2025Article
- Thymic Mimetic Cells: Ontogeny as Immunology.Annual review of cell and developmental biology · 2024Review
- Article
- 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
- Targeting HMGB1: A Potential Therapeutic Strategy for Chronic Kidney Disease.International journal of biological sciences · 2023Review
- Mechanisms of Direct and Indirect Presentation of Self-Antigens in the Thymus.Frontiers in immunology · 2022Review
- Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium.Science immunology · 2021Article
- Regulation of host and viral promoters during human cytomegalovirus latency via US28 and CTCF.The Journal of general virology · 2021Article
- Anti-Inflammatory and Pro-Autophagy Effects of the Cannabinoid Receptor CB2R: Possibility of Modulation in Type 1 Diabetes.Frontiers in pharmacology · 2021Review
- Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence.Frontiers in immunology · 2021Review
- Article
- The Speckled Protein (SP) Family: Immunity's Chromatin Readers.Trends in immunology · 2020Review
- Dual functions of Aire CARD multimerization in the transcriptional regulation of T cell tolerance.Nature communications · 2020Article
- Hassall's corpuscles with cellular-senescence features maintain IFNα production through neutrophils and pDC activation in the thymus.International immunology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA sequencing, we found that inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by the TOP1 inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of γH2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional up-regulation to co-occur with the chromatin structural changes within the genomic cluster of carcinoembryonic antigen-like cellular adhesion molecule genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes.
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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.