title: 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.
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kushagra
authors.initials: K
authors.lastname: Bansal
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D015551:Autoimmunity; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D044127:Epigenesis, Genetic; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000096927:AIRE Protein
chemical_list: D004264:DNA Topoisomerases, Type I; D014157:Transcription Factors; D000096927:AIRE Protein