Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal.
Nat Cell Biol
; 13(7): 762-70, 2011 Jun 19.
Article
em En
| MEDLINE
| ID: mdl-21685894
ABSTRACT
The co-occupancy of Tcf3 with Oct4, Sox2 and Nanog on embryonic stem cell (ESC) chromatin indicated that Tcf3 has been suggested to play an integral role in a poorly understood mechanism underlying Wnt-dependent stimulation of mouse ESC self-renewal of mouse ESCs. Although the conventional view of Tcf proteins as the ß-catenin-binding effectors of Wnt signalling suggested Tcf3-ß-catenin activation of target genes would stimulate self-renewal, here we show that an antagonistic relationship between Wnt3a and Tcf3 on gene expression regulates ESC self-renewal. Genetic ablation of Tcf3 replaced the requirement for exogenous Wnt3a or GSK3 inhibition for ESC self-renewal, demonstrating that inhibition of Tcf3 repressor is the necessary downstream effect of Wnt signalling. Interestingly, both Tcf3-ß-catenin and Tcf1-ß-catenin interactions contributed to Wnt stimulation of self-renewal and gene expression, and the combination of Tcf3 and Tcf1 recruited Wnt-stabilized ß-catenin to Oct4 binding sites on ESC chromatin. This work elucidates the molecular link between the effects of Wnt and the regulation of the Oct4/Sox2/Nanog network.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proliferação de Células
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Proteínas Wnt
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Fator 1-alfa Nuclear de Hepatócito
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Células-Tronco Embrionárias
Limite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos