The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
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DOI：
10.1038/embor.2008.11
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发表时间：
2008-04-01
期刊：
影响因子：
7.7
通讯作者：
Peterson, Paert
中科院分区：
文献类型：
--
作者：
Org, Tonis;Chignola, Francesca;Peterson, Paert
自身免疫调节因子（AIRE）基因突变会导致自身免疫性多内分泌病念珠菌病外胚叶营养不良。AIRE在胸腺髓质上皮细胞中表达，在那里它促进组织限制性抗原的表达。通过生物化学和生物物理学方法的结合使用，我们发现AIRE通过其第一个植物同源结构域（PHD）指（AIRE-PHD 1）选择性地与组蛋白H3相互作用，并优先结合非甲基化的H3 K4（H3 K4 me 0）。因此，体内AIRE结合并激活人胚肾293细胞中含有低水平H3 K4 me 3的启动子。我们的结论是，AIRE-PHD 1是一个新发现的一类PHD手指，特异性识别H3 K4 me 0的重要成员，从而提供了一个新的组蛋白修饰的状态和胸腺中的组织限制性抗原表达的调节之间的联系。
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.