De novo DNA methylation by DNA methyltransferase 3a controls early effector CD8+ T-cell fate decisions following activation.
Proc Natl Acad Sci U S A
; 113(38): 10631-6, 2016 09 20.
Article
en En
| MEDLINE
| ID: mdl-27582468
ABSTRACT
DNMT3a is a de novo DNA methyltransferase expressed robustly after T-cell activation that regulates plasticity of CD4(+) T-cell cytokine expression. Here we show that DNMT3a is critical for directing early CD8(+) T-cell effector and memory fate decisions. Whereas effector function of DNMT3a knockout T cells is normal, they develop more memory precursor and fewer terminal effector cells in a T-cell intrinsic manner compared with wild-type animals. Rather than increasing plasticity of differentiated effector CD8(+) T cells, loss of DNMT3a biases differentiation of early effector cells into memory precursor cells. This is attributed in part to ineffective repression of Tcf1 expression in knockout T cells, as DNMT3a localizes to the Tcf7 promoter and catalyzes its de novo methylation in early effector WT CD8(+) T cells. These data identify DNMT3a as a crucial regulator of CD8(+) early effector cell differentiation and effector versus memory fate decisions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ADN (Citosina-5-)-Metiltransferasas
/
Factor Nuclear 1-alfa del Hepatocito
/
Factor 1 de Transcripción de Linfocitos T
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Memoria Inmunológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2016
Tipo del documento:
Article