Aire mediates the expression of tissue-specific antigens in thymic epithelial cells to promote tolerance against self-reactive T lymphocytes. However, the mechanism that allows expression of tissue-specific genes at levels that prevent harm is unknown. Here we show that Brg1 generates accessibility at tissue-specific loci to impose central tolerance. We found that Aire has an intrinsic repressive function that restricts chromatin accessibility and opposes Brg1 across the genome. Aire exerted this repressive influence within minutes after recruitment to chromatin and restrained the amplitude of active transcription. Disease-causing mutations that impair Aire-induced activation also impair the protein's repressive function, which indicates dual roles for Aire. Together, Brg1 and Aire fine-tune the expression of tissue-specific genes at levels that prevent toxicity yet promote immune tolerance.

中文翻译：

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Aire可以快速抑制染色质，从而可以精确控制免疫耐受性。

Aire介导胸腺上皮细胞中组织特异性抗原的表达，以增强对自身反应性T淋巴细胞的耐受性。但是，尚不知道能够以防止伤害的程度表达组织特异性基因的机制。在这里，我们显示Brg1产生组织特异性基因座处的可及性，以施加中央耐受性。我们发现，Aire具有内在的抑制功能，该功能限制了染色质的可及性并在整个基因组中与Brg1相对。在募集染色质后几分钟内，Aire发挥了这种抑制性作用，并抑制了活性转录的幅度。损害Aire诱导的激活的致病突变也损害了该蛋白的抑制功能，这表明Aire具有双重作用。一起，