Journal
EMBO JOURNAL
Volume 25, Issue 12, Pages 2735-2745Publisher
WILEY
DOI: 10.1038/sj.emboj.7601153
Keywords
Armadillo; CtBP; TCF; wingless; Wnt
Categories
Funding
- NCI NIH HHS [CA95869, R01 CA095869] Funding Source: Medline
- NIGMS NIH HHS [R01 GM059846, R01 GM59846] Funding Source: Medline
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Regulation of Wnt transcriptional targets is thought to occur by a transcriptional switch. In the absence of Wnt signaling, sequence-specific DNA-binding proteins of the TCF family repress Wnt target genes. Upon Wnt stimulation, stabilized beta-catenin binds to TCFs, converting them into transcriptional activators. C-terminal-binding protein ( CtBP) is a transcriptional corepressor that has been reported to inhibit Wnt signaling by binding to TCFs or by preventing beta-catenin from binding to TCF. Here, we show that CtBP is also required for the activation of some Wnt targets in Drosophila. CtBP is recruited to Wnt-regulated enhancers in a Wnt-dependent manner, where it augments Armadillo ( the fly beta-catenin) transcriptional activation. We also found that CtBP is required for repression of a subset of Wnt targets in the absence of Wnt stimulation, but in a manner distinct from previously reported mechanisms. CtBP binds to Wnt-regulated enhancers in a TCF-independent manner and represses target genes in parallel with TCF. Our data indicate dual roles for CtBP as a gene-specific activator and repressor of Wnt target gene transcription.
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