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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 |
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creator | Fang, M Li, J Blauwkamp, T Bhambhani, C Campbell, N Cadigan, K.M |
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. |
doi_str_mv | 10.1038/sj.emboj.7601153 |
format | article |
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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.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/sj.emboj.7601153</identifier><identifier>PMID: 16710294</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>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</subject><ispartof>The EMBO journal, 2006-06, Vol.25 (12), p.2735-2745</ispartof><rights>European Molecular Biology Organization 2006</rights><rights>Copyright © 2006 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Jun 21, 2006</rights><rights>Copyright © 2006, European Molecular Biology Organization 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6943-a332a654353bbeeddca5cf34848d58aed719128f9f0f4a6fe824a7aaab011e7b3</citedby><cites>FETCH-LOGICAL-c6943-a332a654353bbeeddca5cf34848d58aed719128f9f0f4a6fe824a7aaab011e7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1500853/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1500853/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16710294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fang, M</creatorcontrib><creatorcontrib>Li, J</creatorcontrib><creatorcontrib>Blauwkamp, T</creatorcontrib><creatorcontrib>Bhambhani, C</creatorcontrib><creatorcontrib>Campbell, N</creatorcontrib><creatorcontrib>Cadigan, K.M</creatorcontrib><title>C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><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.</description><subject>Alcohol Oxidoreductases</subject><subject>Animals</subject><subject>Armadillo</subject><subject>Armadillo Domain Proteins - metabolism</subject><subject>beta-catenin</subject><subject>Binding sites</subject><subject>C-terminal-binding protein</subject><subject>Cells, Cultured</subject><subject>CtBP</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA-binding proteins</subject><subject>DNA-Binding Proteins - deficiency</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drosophila</subject><subject>Drosophila - cytology</subject><subject>Drosophila - genetics</subject><subject>Drosophila - metabolism</subject><subject>Drosophila melanogaster</subject><subject>Drosophila Proteins - metabolism</subject><subject>EMBO09</subject><subject>enhancer elements</subject><subject>Enhancer Elements, Genetic</subject><subject>Eye - cytology</subject><subject>gene expression regulation</subject><subject>gene induction</subject><subject>gene silencing</subject><subject>Genes</subject><subject>Insects</subject><subject>Models, Biological</subject><subject>Phosphoproteins - deficiency</subject><subject>Phosphoproteins - metabolism</subject><subject>Protein Binding</subject><subject>protein-protein interactions</subject><subject>Proteins</subject><subject>Repressor Proteins - metabolism</subject><subject>Signal Transduction</subject><subject>TCF</subject><subject>TCF Transcription Factors - metabolism</subject><subject>Trans-Activators - deficiency</subject><subject>Trans-Activators - metabolism</subject><subject>transcription (genetics)</subject><subject>transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcriptional Activation - genetics</subject><subject>transcriptional activators</subject><subject>transcriptional corepressors</subject><subject>Wingless</subject><subject>Wnt</subject><subject>Wnt Proteins - metabolism</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkd1v0zAUxSMEYmXwzgsQ8cBbij_i2HlBgnZswPiQtmmP1k1y07lLnWC7g_73GFK1AwntybLO7xwf35skTymZUsLVa7-c4qrql1NZEEoFv5dMaF6QjBEp7icTwgqa5VSVB8kj75eEEKEkfZgc0EJSwsp8kuAsC-hWxkKXVcY2xi7SwfUBjU0b47AO3SaFOpgbCOhTsE3qcHDofbxd2pAGB9bXzgzB9DEkDeAWGHwa_XPX-364Mh08Th600Hl8sj0Pk4v3R-ezk-z06_GH2dvTrC7KnGfAOYNC5FzwqkJsmhpE3fJc5aoRCrCRtKRMtWVL2hyKFhXLQQJAFX-PsuKHyZsxd1hXK2xqtLFepwdnVuA2ugej_1asudKL_kZTQYgSPAa82ga4_vsafdAr42vsOrDYr70uFCUFIexOkErGRCFVBF_-Ay77tYuTikwpmKRcigiREarjyLzDdleZEv1709ov9Z9N6-2mo-X57a_uDdvVRqAcgR-mw82dgfro87uP-3A6en202QW6W6X_X-jZ6LEQ1g53D-71bNSND_hzJ4O71oWMQ9CXX471ydl8Lj99y_V55F-MfAu9hoUzXl-cMUI5oUQpRiX_Bb8b7ZQ</recordid><startdate>20060621</startdate><enddate>20060621</enddate><creator>Fang, M</creator><creator>Li, J</creator><creator>Blauwkamp, T</creator><creator>Bhambhani, C</creator><creator>Campbell, N</creator><creator>Cadigan, K.M</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><scope>FBQ</scope><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7SS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060621</creationdate><title>C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila</title><author>Fang, M ; Li, J ; Blauwkamp, T ; Bhambhani, C ; Campbell, N ; Cadigan, K.M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6943-a332a654353bbeeddca5cf34848d58aed719128f9f0f4a6fe824a7aaab011e7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Alcohol Oxidoreductases</topic><topic>Animals</topic><topic>Armadillo</topic><topic>Armadillo Domain Proteins - metabolism</topic><topic>beta-catenin</topic><topic>Binding sites</topic><topic>C-terminal-binding protein</topic><topic>Cells, Cultured</topic><topic>CtBP</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA-binding proteins</topic><topic>DNA-Binding Proteins - deficiency</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Drosophila</topic><topic>Drosophila - cytology</topic><topic>Drosophila - genetics</topic><topic>Drosophila - metabolism</topic><topic>Drosophila melanogaster</topic><topic>Drosophila Proteins - metabolism</topic><topic>EMBO09</topic><topic>enhancer elements</topic><topic>Enhancer Elements, Genetic</topic><topic>Eye - cytology</topic><topic>gene expression regulation</topic><topic>gene induction</topic><topic>gene silencing</topic><topic>Genes</topic><topic>Insects</topic><topic>Models, Biological</topic><topic>Phosphoproteins - deficiency</topic><topic>Phosphoproteins - metabolism</topic><topic>Protein Binding</topic><topic>protein-protein interactions</topic><topic>Proteins</topic><topic>Repressor Proteins - metabolism</topic><topic>Signal Transduction</topic><topic>TCF</topic><topic>TCF Transcription Factors - metabolism</topic><topic>Trans-Activators - deficiency</topic><topic>Trans-Activators - metabolism</topic><topic>transcription (genetics)</topic><topic>transcription factors</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transcriptional Activation - genetics</topic><topic>transcriptional activators</topic><topic>transcriptional corepressors</topic><topic>Wingless</topic><topic>Wnt</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fang, M</creatorcontrib><creatorcontrib>Li, J</creatorcontrib><creatorcontrib>Blauwkamp, T</creatorcontrib><creatorcontrib>Bhambhani, C</creatorcontrib><creatorcontrib>Campbell, N</creatorcontrib><creatorcontrib>Cadigan, K.M</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest_Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fang, M</au><au>Li, J</au><au>Blauwkamp, T</au><au>Bhambhani, C</au><au>Campbell, N</au><au>Cadigan, K.M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2006-06-21</date><risdate>2006</risdate><volume>25</volume><issue>12</issue><spage>2735</spage><epage>2745</epage><pages>2735-2745</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><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 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.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>16710294</pmid><doi>10.1038/sj.emboj.7601153</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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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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