EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming.
Nat Commun
; 10(1): 3306, 2019 07 24.
Article
em En
| MEDLINE
| ID: mdl-31341159
ABSTRACT
Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8+ T cell innate memory program.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas Nucleares
/
DNA Helicases
/
Linfócitos T CD8-Positivos
/
Proteínas com Domínio T
/
Epigênese Genética
/
Subunidade alfa 3 de Fator de Ligação ao Core
/
Memória Imunológica
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Bélgica