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Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila
Regulation of gene expression by signaling pathways often occurs through a transcriptional switch, where the transcription factor responsible for signal-dependent gene activation represses the same targets in the absence of signaling. T-cell factors (TCFs) are transcription factors in the Wnt/ß-cate...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916239/ https://www.ncbi.nlm.nih.gov/pubmed/24516405 http://dx.doi.org/10.1371/journal.pgen.1004133 |
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author | Bhambhani, Chandan Ravindranath, Aditi J. Mentink, Remco A. Chang, Mikyung V. Betist, Marco C. Yang, Yaxuan X. Koushika, Sandhya P. Korswagen, Hendrik C. Cadigan, Ken M. |
author_facet | Bhambhani, Chandan Ravindranath, Aditi J. Mentink, Remco A. Chang, Mikyung V. Betist, Marco C. Yang, Yaxuan X. Koushika, Sandhya P. Korswagen, Hendrik C. Cadigan, Ken M. |
author_sort | Bhambhani, Chandan |
collection | PubMed |
description | Regulation of gene expression by signaling pathways often occurs through a transcriptional switch, where the transcription factor responsible for signal-dependent gene activation represses the same targets in the absence of signaling. T-cell factors (TCFs) are transcription factors in the Wnt/ß-catenin pathway, which control numerous cell fate specification events in metazoans. The TCF transcriptional switch is mediated by many co-regulators that contribute to repression or activation of Wnt target genes. It is typically assumed that DNA recognition by TCFs is important for target gene location, but plays no role in the actual switch. TCF/Pangolin (the fly TCF) and some vertebrate TCF isoforms bind DNA through two distinct domains, a High Mobility Group (HMG) domain and a C-clamp, which recognize DNA motifs known as HMG and Helper sites, respectively. Here, we demonstrate that POP-1 (the C. elegans TCF) also activates target genes through HMG and Helper site interactions. Helper sites enhanced the ability of a synthetic enhancer to detect Wnt/ß-catenin signaling in several tissues and revealed an unsuspected role for POP-1 in regulating the C. elegans defecation cycle. Searching for HMG-Helper site clusters allowed the identification of a new POP-1 target gene active in the head muscles and gut. While Helper sites and the C-clamp are essential for activation of worm and fly Wnt targets, they are dispensable for TCF-dependent repression of targets in the absence of Wnt signaling. These data suggest that a fundamental change in TCF-DNA binding contributes to the transcriptional switch that occurs upon Wnt stimulation. |
format | Online Article Text |
id | pubmed-3916239 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39162392014-02-10 Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila Bhambhani, Chandan Ravindranath, Aditi J. Mentink, Remco A. Chang, Mikyung V. Betist, Marco C. Yang, Yaxuan X. Koushika, Sandhya P. Korswagen, Hendrik C. Cadigan, Ken M. PLoS Genet Research Article Regulation of gene expression by signaling pathways often occurs through a transcriptional switch, where the transcription factor responsible for signal-dependent gene activation represses the same targets in the absence of signaling. T-cell factors (TCFs) are transcription factors in the Wnt/ß-catenin pathway, which control numerous cell fate specification events in metazoans. The TCF transcriptional switch is mediated by many co-regulators that contribute to repression or activation of Wnt target genes. It is typically assumed that DNA recognition by TCFs is important for target gene location, but plays no role in the actual switch. TCF/Pangolin (the fly TCF) and some vertebrate TCF isoforms bind DNA through two distinct domains, a High Mobility Group (HMG) domain and a C-clamp, which recognize DNA motifs known as HMG and Helper sites, respectively. Here, we demonstrate that POP-1 (the C. elegans TCF) also activates target genes through HMG and Helper site interactions. Helper sites enhanced the ability of a synthetic enhancer to detect Wnt/ß-catenin signaling in several tissues and revealed an unsuspected role for POP-1 in regulating the C. elegans defecation cycle. Searching for HMG-Helper site clusters allowed the identification of a new POP-1 target gene active in the head muscles and gut. While Helper sites and the C-clamp are essential for activation of worm and fly Wnt targets, they are dispensable for TCF-dependent repression of targets in the absence of Wnt signaling. These data suggest that a fundamental change in TCF-DNA binding contributes to the transcriptional switch that occurs upon Wnt stimulation. Public Library of Science 2014-02-06 /pmc/articles/PMC3916239/ /pubmed/24516405 http://dx.doi.org/10.1371/journal.pgen.1004133 Text en © 2014 Bhambhani et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bhambhani, Chandan Ravindranath, Aditi J. Mentink, Remco A. Chang, Mikyung V. Betist, Marco C. Yang, Yaxuan X. Koushika, Sandhya P. Korswagen, Hendrik C. Cadigan, Ken M. Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila |
title | Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila
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title_full | Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila
|
title_fullStr | Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila
|
title_full_unstemmed | Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila
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title_short | Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in C. elegans and Drosophila
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title_sort | distinct dna binding sites contribute to the tcf transcriptional switch in c. elegans and drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916239/ https://www.ncbi.nlm.nih.gov/pubmed/24516405 http://dx.doi.org/10.1371/journal.pgen.1004133 |
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