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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 en 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.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Linfocitos T Reguladores / Autotolerancia / Proteínas de Unión a la Región de Fijación a la Matriz / Ensamble y Desensamble de Cromatina / Factores de Transcripción Forkhead Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Linfocitos T Reguladores / Autotolerancia / Proteínas de Unión a la Región de Fijación a la Matriz / Ensamble y Desensamble de Cromatina / Factores de Transcripción Forkhead Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Alemania