Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.
Nat Immunol
; 12(9): 898-907, 2011 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-21841785
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Linfócitos T Reguladores
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Tolerância a Antígenos Próprios
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Proteínas de Ligação à Região de Interação com a Matriz
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Montagem e Desmontagem da Cromatina
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Fatores de Transcrição Forkhead
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha