Journal
EMBO REPORTS
Volume 9, Issue 4, Pages 370-376Publisher
WILEY
DOI: 10.1038/embor.2008.11
Keywords
AIRE; negative selection; NMR; protein structure
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Funding
- Telethon [TCP99035] Funding Source: Medline
- Wellcome Trust [067503] Funding Source: Medline
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Mutations in the gene autoimmune regulator ( AIRE) cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of tissue-restricted antigens. By the combined use of biochemical and biophysical methods, we show that AIRE selectively interacts with histone H3 through its first plant homeodomain (PHD) finger (AIRE-PHD1) and preferentially binds to non-methylated H3K4 (H3K4me0). Accordingly, in vivo AIRE binds to and activates promoters containing low levels of H3K4me3 in human embryonic kidney 293 cells. We conclude that AIRE-PHD1 is an important member of a newly identified class of PHD fingers that specifically recognize H3K4me0, thus providing a new link between the status of histone modifications and the regulation of tissue-restricted antigen expression in thymus.
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