title: The autoimmune regulator directly controls the expression of genes critical for thymic epithelial function.
abstract: The autoimmune regulator (Aire) gene plays an essential role in negative selection of T cells and deletion of autoreactive T cells in the thymus. The defect in thymic selection in Aire(-/-) mice was attributed to the repressed expression of tissue-specific Ags in the thymic epithelial cells and defective Ag presentation; however, the molecular mechanism underlying these functions has been elusive. Using the chromatin immunoprecipitation technique, we demonstrate here that Aire binds in vivo to specific DNA sequence motifs and directly regulates thymic expression of genes important for thymic functions including expression of autoantigens, cytokines, transcription factors, and posttranslational modifiers. These results unambiguously established Aire as a key transcriptional regulator of the immune system.
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Ruan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tung
authors.forename: Daniel
authors.initials: D
authors.lastname: Eisenman
authors.forename: Yulius
authors.initials: Y
authors.lastname: Setiady
authors.forename: Sarah
authors.initials: S
authors.lastname: Eckenrode
authors.forename: Bing
authors.initials: B
authors.lastname: Yi
authors.forename: Sharad
authors.initials: S
authors.lastname: Purohit
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D016130:Immunophenotyping; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D014157:Transcription Factors; D000096927:AIRE Protein