title: Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.
abstract: Regulatory T cells (T(reg) cells) are essential for self-tolerance and immune homeostasis. Lack of effector T cell (T(eff) cell) function and gain of suppressive activity by T(reg) cells are dependent on the transcriptional program induced by Foxp3. Here we report that repression of SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells. Foxp3, acting as a transcriptional repressor, directly suppressed the SATB1 locus and indirectly suppressed it through the induction of microRNAs that bound the SATB1 3' untranslated region. Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines. Our data support the proposal that inhibition of SATB1-mediated modulation of global chromatin remodeling is pivotal for maintaining T(reg) cell functionality.
authors.affiliation: Life and Medical Sciences Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.forename: Yasser
authors.initials: Y
authors.lastname: Thabet
authors.forename: Roman-Ulrich
authors.initials: RU
authors.lastname: Müller
authors.forename: Timothy
authors.initials: T
authors.lastname: Sadlon
authors.forename: Sabine
authors.initials: S
authors.lastname: Classen
authors.forename: Katharina
authors.initials: K
authors.lastname: Lahl
authors.forename: Samik
authors.initials: S
authors.lastname: Basu
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhou
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Bailey-Bucktrout
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Krebs
authors.forename: Eva A
authors.initials: EA
authors.lastname: Schönfeld
authors.forename: Jan
authors.initials: J
authors.lastname: Böttcher
authors.forename: Tatiana
authors.initials: T
authors.lastname: Golovina
authors.forename: Christian T
authors.initials: CT
authors.lastname: Mayer
authors.forename: Andrea
authors.initials: A
authors.lastname: Hofmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Sommer
authors.forename: Svenja
authors.initials: S
authors.lastname: Debey-Pascher
authors.forename: Elmar
authors.initials: E
authors.lastname: Endl
authors.forename: Andreas
authors.initials: A
authors.lastname: Limmer
authors.forename: Keli L
authors.initials: KL
authors.lastname: Hippen
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Robert
authors.initials: R
authors.lastname: Balderas
authors.forename: Thomas
authors.initials: T
authors.lastname: Quast
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha
authors.forename: Günter
authors.initials: G
authors.lastname: Mayer
authors.forename: Michael
authors.initials: M
authors.lastname: Famulok
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schermer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Simon C
authors.initials: SC
authors.lastname: Barry
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: James L
authors.initials: JL
authors.lastname: Riley
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D016086:Lentivirus; D008213:Lymphocyte Activation / Q000187:drug effects; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D020413:3' Untranslated Regions; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D036961:Matrix Attachment Region Binding Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; C076189:SATB1 protein, human