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 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.
Fang
Ming
M
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Li
Jiong
J
Blauwkamp
Timothy
T
Bhambhani
Chandan
C
Campbell
Nathan
N
Cadigan
Ken M
KM
D000429:Alcohol Oxidoreductases; D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005123:Eye / Q000166:cytology; D008954:Models, Biological; D010750:Phosphoproteins / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism*
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein