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PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.
Gamble, Noah; Bradu, Alexandra; Caldwell, Jason A; McKeever, Joshua; Bolonduro, Olubusayo; Ermis, Ebru; Kaiser, Caroline; Kim, YeEun; Parks, Benjamin; Klemm, Sandy; Greenleaf, William J; Crabtree, Gerald R; Koh, Andrew S.
Afiliación
  • Gamble N; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Bradu A; Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL, USA.
  • Caldwell JA; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • McKeever J; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Bolonduro O; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Ermis E; Committee on Molecular Metabolism and Nutrition, University of Chicago, Chicago, IL, USA.
  • Kaiser C; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Kim Y; Committee on Genetics, Genomics, Systems Biology, University of Chicago, Chicago, IL, USA.
  • Parks B; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Klemm S; Department of Pathology, University of Chicago, Chicago, IL, USA.
  • Greenleaf WJ; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Crabtree GR; Immunology Program, Stanford University, Stanford, CA, USA.
  • Koh AS; Department of Genetics, Stanford University, Stanford, CA, USA.
Nat Immunol ; 25(5): 860-872, 2024 May.
Article en En | MEDLINE | ID: mdl-38632339
ABSTRACT
Adaptive immunity relies on specialized effector functions elicited by lymphocytes, yet how antigen recognition activates appropriate effector responses through nonspecific signaling intermediates is unclear. Here we examined the role of chromatin priming in specifying the functional outputs of effector T cells and found that most of the cis-regulatory landscape active in effector T cells was poised early in development before the expression of the T cell antigen receptor. We identified two principal mechanisms underpinning this poised landscape the recruitment of the nucleosome remodeler mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) by the transcription factors RUNX1 and PU.1 to establish chromatin accessibility at T effector loci; and a 'relay' whereby the transcription factor BCL11B succeeded PU.1 to maintain occupancy of the chromatin remodeling complex mSWI/SNF together with RUNX1, after PU.1 silencing during lineage commitment. These mechanisms define modes by which T cells acquire the potential to elicit specialized effector functions early in their ontogeny and underscore the importance of integrating extrinsic cues to the developmentally specified intrinsic program.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Represoras / Factores de Transcripción / Transactivadores / Proteínas Proto-Oncogénicas / Proteínas Supresoras de Tumor / Subunidad alfa 2 del Factor de Unión al Sitio Principal Límite: Animals Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Represoras / Factores de Transcripción / Transactivadores / Proteínas Proto-Oncogénicas / Proteínas Supresoras de Tumor / Subunidad alfa 2 del Factor de Unión al Sitio Principal Límite: Animals Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos