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Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation

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dc.contributor.authorBeyer, M.
dc.contributor.authorSadlon, T.
dc.contributor.authorBarry, S.
dc.date.issued2011
dc.description.abstractRegulatory 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.
dc.description.statementofresponsibilityMarc Beyer... Timothy Sadlon...Simon C Barry... et al.
dc.identifier.citationNature Immunology, 2011; 12(9):898-907
dc.identifier.doi10.1038/ni.2084
dc.identifier.issn1529-2908
dc.identifier.issn1529-2916
dc.identifier.orcidSadlon, T. [0000-0002-4821-2462]
dc.identifier.orcidBarry, S. [0000-0002-0597-7609]
dc.identifier.urihttp://hdl.handle.net/2440/66904
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/399123
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/565314
dc.rights© 2011 Nature America, Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1038/ni.2084
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectHumans
dc.subjectMice
dc.subjectLentivirus
dc.subjectMatrix Attachment Region Binding Proteins
dc.subjectMicroRNAs
dc.subjectRNA, Small Interfering
dc.subject3' Untranslated Regions
dc.subjectFlow Cytometry
dc.subjectGene Expression Profiling
dc.subjectTransduction, Genetic
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectLymphocyte Activation
dc.subjectCell Differentiation
dc.subjectChromatin Assembly and Disassembly
dc.subjectSelf Tolerance
dc.subjectGene Expression Regulation
dc.subjectRNA Interference
dc.subjectGenome, Human
dc.subjectT-Lymphocytes, Regulatory
dc.subjectForkhead Transcription Factors
dc.subjectGenome-Wide Association Study
dc.titleRepression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation
dc.typeJournal article
pubs.publication-statusPublished

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