Sp5 and Sp8 recruit ß-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription.
Proc Natl Acad Sci U S A
; 113(13): 3545-50, 2016 Mar 29.
Article
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| MEDLINE
| ID: mdl-26969725
ABSTRACT
The ancient, highly conserved, Wnt signaling pathway regulates cell fate in all metazoans. We have previously shown that combined null mutations of the specificity protein (Sp) 1/Klf-like zinc-finger transcription factors Sp5 and Sp8 (i.e., Sp5/8) result in an embryonic phenotype identical to that observed when core components of the Wnt/ß-catenin pathway are mutated; however, their role in Wnt signal transduction is unknown. Here, we show in mouse embryos and differentiating embryonic stem cells that Sp5/8 are gene-specific transcriptional coactivators in the Wnt/ß-catenin pathway. Sp5/8 bind directly to GC boxes in Wnt target gene enhancers and to adjacent, or distally positioned, chromatin-bound T-cell factor (Tcf) 1/lymphoid enhancer factor (Lef) 1 to facilitate recruitment of ß-catenin to target gene enhancers. Because Sp5 is itself directly activated by Wnt signals, we propose that Sp5 is a Wnt/ß-catenin pathway-specific transcript on factor that functions in a feed-forward loop to robustly activate select Wnt target genes.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Proteínas de Unión al ADN
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Beta Catenina
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Factor Nuclear 1-alfa del Hepatocito
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Factor de Unión 1 al Potenciador Linfoide
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Vía de Señalización Wnt
Límite:
Animals
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Pregnancy
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2016
Tipo del documento:
Article