title: Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment.
abstract: Most Foxp3+regulatory T (Treg) cells develop in the thymus as a functionally mature T cell subpopulation specialized for immune suppression. Their cell fate appears to be determined before Foxp3 expression; yet molecular events that prime Foxp3-Tregprecursor cells are largely obscure. We found that Tregcell-specific super-enhancers (Treg-SEs), which were associated with Foxp3 and other Tregcell signature genes, began to be activated in Tregprecursor cells. T cell-specific deficiency of the genome organizer Satb1 impaired Treg-SE activation and the subsequent expression of Tregsignature genes, causing severe autoimmunity due to Tregcell deficiency. These results suggest that Satb1-dependent Treg-SE activation is crucial for Tregcell lineage specification in the thymus and that its perturbation is causative of autoimmune and other immunological diseases.
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.|Laboratory of Experimental Immunology, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Naganari
authors.initials: N
authors.lastname: Ohkura
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Kidani
authors.affiliation: Immuno-Genomics Research Unit, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vandenbon
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.|Laboratory of Integrative Biological Science, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirota
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kawakami
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.|Laboratory of Experimental Immunology, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Motooka
authors.affiliation: Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Immunology, School of Medicine, Toho University, Tokyo, Japan.
authors.forename: Motonari
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Laboratory for Transcriptional Regulation, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Terumi
authors.initials: T
authors.lastname: Kohwi-Shigematsu
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.|Laboratory of Experimental Immunology, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000235:genetics; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007108:Immune Tolerance; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D054504:Precursor Cells, T-Lymphoid / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D015533:Transcriptional Activation / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D036961:Matrix Attachment Region Binding Proteins; C469541:Satb1 protein, mouse