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Natural Genetic Variation Reveals Key Features of Epigenetic and Transcriptional Memory in Virus-Specific CD8 T Cells.
van der Veeken, Joris; Zhong, Yi; Sharma, Roshan; Mazutis, Linas; Dao, Phuong; Pe'er, Dana; Leslie, Christina S; Rudensky, Alexander Y.
Afiliação
  • van der Veeken J; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Zhong Y; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational and Systems Biology Program, Memorial S
  • Sharma R; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY, USA.
  • Mazutis L; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Dao P; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Pe'er D; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Leslie CS; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Rudensky AY; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: rudenska@mskcc.org.
Immunity ; 50(5): 1202-1217.e7, 2019 05 21.
Article em En | MEDLINE | ID: mdl-31027997
Stable changes in chromatin states and gene expression in cells of the immune system form the basis for memory of infections and other challenges. Here, we used naturally occurring cis-regulatory variation in wild-derived inbred mouse strains to explore the mechanisms underlying long-lasting versus transient gene regulation in CD8 T cells responding to acute viral infection. Stably responsive DNA elements were characterized by dramatic and congruent chromatin remodeling events affecting multiple neighboring sites and required distinct transcription factor (TF) binding motifs for their accessibility. Specifically, we found that cooperative recruitment of T-box and Runx family transcription factors to shared targets mediated stable chromatin remodeling upon T cell activation. Our observations provide insights into the molecular mechanisms driving virus-specific CD8 T cell responses and suggest a general mechanism for the formation of transcriptional and epigenetic memory applicable to other immune and non-immune cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Linfócitos T CD8-Positivos / Proteínas com Domínio T / Montagem e Desmontagem da Cromatina / Subunidade alfa 2 de Fator de Ligação ao Core / Coriomeningite Linfocítica / Vírus da Coriomeningite Linfocítica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Linfócitos T CD8-Positivos / Proteínas com Domínio T / Montagem e Desmontagem da Cromatina / Subunidade alfa 2 de Fator de Ligação ao Core / Coriomeningite Linfocítica / Vírus da Coriomeningite Linfocítica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos