Centromeric repositioning of coreceptor loci predicts their stable silencing and the CD4/CD8 lineage choice.
J Exp Med
; 200(11): 1437-44, 2004 Dec 06.
Article
em En
| MEDLINE
| ID: mdl-15583016
ABSTRACT
The differentiation of CD4(+) CD8(+) double positive (DP) thymocytes requires the irreversible choice between two alternative lineages, distinguished by the mutually exclusive expression of either CD4 or CD8. Differentiating DP cells transiently down-regulate both CD4 and CD8, and this has complicated the debate whether the mechanism of CD4/CD8 lineage choice is instructive, stochastic/selective, or more complex in nature. Using fluorescence in situ hybridization, we show that the stable silencing of coreceptor loci, and ultimately lineage choice, is predicted by the spatial repositioning of coreceptor alleles to centromeric heterochromatin domains. These data provide evidence that lineage-specific developmental programs are established early during the transition from the DP to the single positive stage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antígenos CD4
/
Centrômero
/
Antígenos CD8
/
Linhagem da Célula
/
Inativação Gênica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article