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The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression.

ABSTRACT: 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.

SUBMITTER: Org T

PROVIDER: S-EPMC2261226 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Structure and site-specific recognition of histone H3 by the PHD finger of human autoimmune regulator.

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