Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/66904
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Type: Journal article
Title: Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation
Author: Beyer, M.
Sadlon, T.
Barry, S.
Citation: Nature Immunology, 2011; 12(9):898-907
Publisher: Nature Publishing Group
Issue Date: 2011
ISSN: 1529-2908
1529-2916
Statement of
Responsibility: 
Marc Beyer... Timothy Sadlon...Simon C Barry... et al.
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.
Keywords: Animals; Mice, Inbred C57BL; Mice, Knockout; Humans; Mice; Lentivirus; Matrix Attachment Region Binding Proteins; MicroRNAs; RNA, Small Interfering; 3' Untranslated Regions; Flow Cytometry; Gene Expression Profiling; Transduction, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Lymphocyte Activation; Cell Differentiation; Chromatin Assembly and Disassembly; Self Tolerance; Gene Expression Regulation; RNA Interference; Genome, Human; T-Lymphocytes, Regulatory; Forkhead Transcription Factors; Genome-Wide Association Study
Rights: © 2011 Nature America, Inc. All rights reserved.
RMID: 0020112428
DOI: 10.1038/ni.2084
Grant ID: http://purl.org/au-research/grants/nhmrc/399123
http://purl.org/au-research/grants/nhmrc/565314
Appears in Collections:Microbiology and Immunology publications

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