AIRE recruits multiple transcriptional components to specific genomic regions through tethering to nuclear matrix

• Published in: Molecular immunology Vol. 43; no. 4; pp. 335 - 345
• Main Authors: Tao, Yunxia, Kupfer, Rene, Stewart, Benjamin J., Williams-Skipp, Cheryll, Crowell, Christopher K., Patel, Dhavalkumar D., Sain, Steven, Scheinman, Robert I.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2006
• Subjects: AIRE; AIRE Protein; Animals; Antigen Presentation; Autoantigens - immunology; Autoimmunity; Base Sequence; Carrier Proteins - metabolism; Chlorocebus aethiops; Chromosome Mapping; Corticosterone; COS Cells; DNA, Complementary - genetics; Gene Expression Profiling; Genes, Synthetic; Humans; Intracellular Signaling Peptides and Proteins - physiology; Macromolecular Substances; Mice; Molecular Sequence Data; NF-kappa B - metabolism; Nuclear matrix; Nuclear Matrix - physiology; Protein Interaction Mapping; Protein Structure, Tertiary; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - physiology; Self Tolerance - physiology; Sequence Homology, Nucleic Acid; Stromal Cells - immunology; Thymus Gland - immunology; Thymus Gland - metabolism; Transcription; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic - physiology; Transfection; Two-Hybrid System Techniques; Ubiquitin-Protein Ligases; Zinc Fingers - physiology; Autoimmunity; Transcription; AIRE; Nuclear matrix
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2005.02.018

Thymic selection requires that diverse self antigens be presented to developing thymocytes by stromal cells. Consistent with this function, medullary thymic epithelial cells have been shown to express a large number of genes, many of which are tissue restricted. Autoimmune regulator (AIRE) is a nuclear protein, which has recently been identified as a regulator of this process, however, the mechanism by which AIRE functions is not well understood. Here we use a transrepression assay to demonstrate that AIRE interacts with multiple components of the transcription complex including a novel interaction with the UBA domain protein, GBDR1. When AIRE is expressed in cultured human thymic epithelial cells, it tightly associates with nuclear matrix, suggesting that AIRE responsive genes may be localized to specific regions. Using a mathematical approach we have re-analyzed an Affymetrix dataset identifying AIRE responsive genes and show that they tend to localize to specific regions of the genome. Together, these data suggest that AIRE regulates gene expression by recruiting components of the transcription complex to specific regions of the genome via interactions with nuclear matrix.