An ancient Pygo-dependent Wnt enhanceosome integrated by Chip/LDB-SSDP.
Elife
; 42015 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-26312500
ABSTRACT
TCF/LEF factors are ancient context-dependent enhancer-binding proteins that are activated by ß-catenin following Wnt signaling. They control embryonic development and adult stem cell compartments, and their dysregulation often causes cancer. ß-catenin-dependent transcription relies on the NPF motif of Pygo proteins. Here, we use a proteomics approach to discover the Chip/LDB-SSDP (ChiLS) complex as the ligand specifically binding to NPF. ChiLS also recognizes NPF motifs in other nuclear factors including Runt/RUNX2 and Drosophila ARID1, and binds to Groucho/TLE. Studies of Wnt-responsive dTCF enhancers in the Drosophila embryonic midgut indicate how these factors interact to form the Wnt enhanceosome, primed for Wnt responses by Pygo. Together with previous evidence, our study indicates that ChiLS confers context-dependence on TCF/LEF by integrating multiple inputs from lineage and signal-responsive factors, including enhanceosome switch-off by Notch. Its pivotal function in embryos and stem cells explain why its integrity is crucial in the avoidance of cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Fatores de Transcrição
/
Proteínas Nucleares
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Proteínas de Drosophila
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Peptídeos e Proteínas de Sinalização Intracelular
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Drosophila
/
Via de Sinalização Wnt
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2015
Tipo de documento:
Article