The transcriptional regulator Aire binds to and activates super-enhancers

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.