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C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila

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 β‐catenin binds to TCFs, converting them into transcriptiona...

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Published in:The EMBO journal 2006-06, Vol.25 (12), p.2735-2745
Main Authors: Fang, M, Li, J, Blauwkamp, T, Bhambhani, C, Campbell, N, Cadigan, K.M
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cited_by cdi_FETCH-LOGICAL-c6943-a332a654353bbeeddca5cf34848d58aed719128f9f0f4a6fe824a7aaab011e7b3
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description 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 β‐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 β‐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 β‐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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subjects Alcohol Oxidoreductases
Animals
Armadillo
Armadillo Domain Proteins - metabolism
beta-catenin
Binding sites
C-terminal-binding protein
Cells, Cultured
CtBP
Deoxyribonucleic acid
DNA
DNA-binding proteins
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - metabolism
Drosophila
Drosophila - cytology
Drosophila - genetics
Drosophila - metabolism
Drosophila melanogaster
Drosophila Proteins - metabolism
EMBO09
enhancer elements
Enhancer Elements, Genetic
Eye - cytology
gene expression regulation
gene induction
gene silencing
Genes
Insects
Models, Biological
Phosphoproteins - deficiency
Phosphoproteins - metabolism
Protein Binding
protein-protein interactions
Proteins
Repressor Proteins - metabolism
Signal Transduction
TCF
TCF Transcription Factors - metabolism
Trans-Activators - deficiency
Trans-Activators - metabolism
transcription (genetics)
transcription factors
Transcription Factors - metabolism
Transcription, Genetic
Transcriptional Activation - genetics
transcriptional activators
transcriptional corepressors
Wingless
Wnt
Wnt Proteins - metabolism
title C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila
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