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The transcriptional regulator Aire binds to and activates super-enhancers.


ABSTRACT: 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. We found that Aire and some of its partners, notably those implicated in the DNA-damage response, preferentially localized to and activated long chromatin stretches that were overloaded with transcriptional regulators, known as super-enhancers. We also identified topoisomerase 1 as a cardinal Aire partner that colocalized 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.

SUBMITTER: Bansal K 

PROVIDER: S-EPMC5310976 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The transcriptional regulator Aire binds to and activates super-enhancers.

Bansal Kushagra K   Yoshida Hideyuki H   Benoist Christophe C   Mathis Diane D  

Nature immunology 20170130 3


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. We found that Aire and some of its partners, notably those implicated in the DNA-damage response, preferentially localized to and activated long chromatin stretches that were overloaded with transcriptional regulators, known as super-enhancers. We also identified to  ...[more]

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