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The transcriptional regulator Aire binds to and activates super-enhancers

by Mathis, Diane , Bansal, Kushagra , Yoshida, Hideyuki , Benoist, Christophe

in 38 / 45 / 45/61 / 631/250/2502/2170 / 631/250/38 / 82 / 82/1 / AIRE Protein / Animals / Autoimmunity / Biomedicine / Chromatin / Chromatin Assembly and Disassembly / DNA / DNA damage / DNA Damage - genetics / DNA repair / DNA Repair - genetics / DNA Topoisomerases, Type I - genetics / DNA Topoisomerases, Type I - metabolism / Enhancer Elements, Genetic - physiology / Epigenesis, Genetic / Gene Regulatory Networks / Genes / Genomes / Health aspects / HEK293 Cells / Humans / Immune Tolerance / Immunogenetics / Immunologic research / Immunology / Infectious Diseases / Mice / Mice, Inbred C57BL / Mice, Knockout / Physiological aspects / Protein Binding / T cells / T-Lymphocytes - physiology / Thymus Gland - physiology / Topoisomerase I / Transcription (Genetics) / Transcription factors / Transcription Factors - genetics / Transcription Factors - metabolism / Transcriptional Activation

2017

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The transcriptional regulator Aire binds to and activates super-enhancers

by Mathis, Diane , Bansal, Kushagra , Yoshida, Hideyuki , Benoist, Christophe

2017

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The transcriptional regulator Aire binds to and activates super-enhancers

by Mathis, Diane , Bansal, Kushagra , Yoshida, Hideyuki , Benoist, Christophe

2017

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Journal Article

The transcriptional regulator Aire binds to and activates super-enhancers

Mathis, Diane,

Bansal, Kushagra,

Yoshida, Hideyuki,

Benoist, Christophe

2017

Overview

Mathis and colleagues show that the transcriptional regulator Aire preferentially localizes in 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. 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.

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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

/ 45

/ 45/61

/ 631/250/2502/2170

/ 631/250/38

/ 82

/ 82/1

/ AIRE Protein