ArticleProceedings of the National Academy of Sciences of the United States of America2013
Aire's plant homeodomain(PHD)-2 is critical for induction of immunological tolerance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- A novel heterozygous pathogenicJournal of human immunity · 2025Article
- Aire Mutations and Autoimmune Diseases.Advances in experimental medicine and biology · 2025Review
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- Case Report: Clinical and molecular features of a radiosensitive autoimmune polyendocrine syndrome type 1 patient with oral carcinoma.Frontiers in genetics · 2025Article
- High-resolution transcriptional impact of AIRE: effects of pathogenic variants p.Arg257Ter, p.Cys311Tyr, and polygenic risk variant p.Arg471Cys.Frontiers in immunology · 2025Article
- Mechanism for controlled assembly of transcriptional condensates by Aire.Nature immunology · 2024Article
- Spectrum of germline AIRE mutations causing APS-1 and familial hypoparathyroidism.European journal of endocrinology · 2022Article
- A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1.Frontiers in cell and developmental biology · 2022Article
- Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation.The Journal of experimental medicine · 2021Article
- Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on superenhancers.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genome-wide association study identifies five risk loci for pernicious anemia.Nature communications · 2021Article
- Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence.Frontiers in immunology · 2021Review
- The Autoimmune Regulator (Aire) transactivates HLA-G gene expression in thymic epithelial cells.Immunology · 2019Article
- Twenty Years of AIRE.Frontiers in immunology · 2018Review
- The transcriptional regulator Aire binds to and activates super-enhancers.Nature immunology · 2017Article
- 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
- Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.Genome research · 2014Article
- A novel mutation in autoimmune regulator gene causes autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.Journal of endocrinological investigation · 2014Article
- An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Aire impacts immunological tolerance by regulating the expression of a large set of genes in thymic medullary epithelial cells, thereby controlling the repertoire of self-antigens encountered by differentiating thymocytes. Both humans and mice lacking Aire develop multiorgan autoimmunity. Currently, there are few molecular details on how Aire performs this crucial function. The more amino-terminal of its two plant homeodomains (PHDs), PHD1, helps Aire target poorly transcribed loci by "reading" the methylation status of a particular lysine residue of histone-3, a process that does not depend on the more carboxyl-terminal PHD-2. This study addresses the role of PHD2 in Aire function by comparing the behavior of wild-type and PHD2-deleted Aire in both transfected cells and transgenic mice. PHD2 was required for Aire to interact with sets of protein partners involved in chromatin structure/binding or transcription but not with those implicated in pre-mRNA processing; it also was not required for Aire's nuclear translocation or regional distribution. PHD2 strongly influenced the ability of Aire to regulate the medullary epithelial cell transcriptome and so was crucial for effective central tolerance induction. Thus, Aire's two PHDs seem to play distinct roles in the scenario by which it assures immunological tolerance.
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