title: C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Fang
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Timothy
authors.initials: T
authors.lastname: Blauwkamp
authors.forename: Chandan
authors.initials: C
authors.lastname: Bhambhani
authors.forename: Nathan
authors.initials: N
authors.lastname: Campbell
authors.forename: Ken M
authors.initials: KM
authors.lastname: Cadigan
mesh_terms: 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*
chemical_list: 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