The transcriptional regulator Aire binds to and activates super-enhancers.
The transcriptional regulator Aire binds to and activates super-enhancers.
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DOI：
10.1038/ni.3675
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发表时间：
2017-03
影响因子：
30.5
通讯作者：
Mathis D
中科院分区：
文献类型：
--
作者：
Bansal K;Yoshida H;Benoist C;Mathis D
Aire 是一种转录因子，通过诱导胸腺基质细胞中大量基因的表达来控制 T 细胞耐受性。它与多种不同功能类别的蛋白质伙伴相互作用。在这里，我们表明，Aire 及其一些伙伴，特别是那些与 DNA 损伤反应有关的伙伴，优先定位于并激活了超载转录调节因子的长染色质片段，称为“超级增强子”。我们还确定拓扑异构酶 1 是主要的 Aire 伙伴，它共定位于超级增强子上，并且是 Aire 与其所有其他伙伴相互作用所必需的。我们提出了一个需要超级增强子循环的模型，以有效地将含有 Aire 的复合物传递到局部和远端转录起始位点。
Aire is a transcription factor that controls T cell tolerance by inducing the expression of a large repertoire of genes specifically in thymic stromal cells. It interacts with scores of protein partners of diverse functional classes. Here we showed that Aire and some of its partners, notably those implicated in the DNA-damage response, preferentially localized within and activated long chromatin stretches overloaded with transcriptional regulators, known as “super-enhancers”. We also identified topoisomerase 1 as a cardinal Aire partner that co-localized on super-enhancers and was required for the interaction of Aire with all of its other associates. We propose a model that entails looping of super-enhancers to efficiently deliver Aire-containing complexes to local and distal transcriptional start sites.