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A conserved role for Snail as a potentiator of active transcription

The transcription factors of the Snail family are key regulators of epithelial–mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila ∼25 years ago, Snail has been extensively studied for its role as a transcriptional repressor. Here we demonstrate that...

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Autores principales: Rembold, Martina, Ciglar, Lucia, Yáñez-Cuna, J. Omar, Zinzen, Robert P., Girardot, Charles, Jain, Ankit, Welte, Michael A., Stark, Alexander, Leptin, Maria, Furlong, Eileen E.M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909790/
https://www.ncbi.nlm.nih.gov/pubmed/24402316
http://dx.doi.org/10.1101/gad.230953.113
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author Rembold, Martina
Ciglar, Lucia
Yáñez-Cuna, J. Omar
Zinzen, Robert P.
Girardot, Charles
Jain, Ankit
Welte, Michael A.
Stark, Alexander
Leptin, Maria
Furlong, Eileen E.M.
author_facet Rembold, Martina
Ciglar, Lucia
Yáñez-Cuna, J. Omar
Zinzen, Robert P.
Girardot, Charles
Jain, Ankit
Welte, Michael A.
Stark, Alexander
Leptin, Maria
Furlong, Eileen E.M.
author_sort Rembold, Martina
collection PubMed
description The transcription factors of the Snail family are key regulators of epithelial–mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila ∼25 years ago, Snail has been extensively studied for its role as a transcriptional repressor. Here we demonstrate that Drosophila Snail can positively modulate transcriptional activation. By combining information on in vivo occupancy with expression profiling of hand-selected, staged snail mutant embryos, we identified 106 genes that are potentially directly regulated by Snail during mesoderm development. In addition to the expected Snail-repressed genes, almost 50% of Snail targets showed an unanticipated activation. The majority of “Snail-activated” genes have enhancer elements cobound by Twist and are expressed in the mesoderm at the stages of Snail occupancy. Snail can potentiate Twist-mediated enhancer activation in vitro and is essential for enhancer activity in vivo. Using a machine learning approach, we show that differentially enriched motifs are sufficient to predict Snail's regulatory response. In silico mutagenesis revealed a likely causative motif, which we demonstrate is essential for enhancer activation. Taken together, these data indicate that Snail can potentiate enhancer activation by collaborating with different activators, providing a new mechanism by which Snail regulates development.
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spelling pubmed-39097902014-07-15 A conserved role for Snail as a potentiator of active transcription Rembold, Martina Ciglar, Lucia Yáñez-Cuna, J. Omar Zinzen, Robert P. Girardot, Charles Jain, Ankit Welte, Michael A. Stark, Alexander Leptin, Maria Furlong, Eileen E.M. Genes Dev Research Paper The transcription factors of the Snail family are key regulators of epithelial–mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila ∼25 years ago, Snail has been extensively studied for its role as a transcriptional repressor. Here we demonstrate that Drosophila Snail can positively modulate transcriptional activation. By combining information on in vivo occupancy with expression profiling of hand-selected, staged snail mutant embryos, we identified 106 genes that are potentially directly regulated by Snail during mesoderm development. In addition to the expected Snail-repressed genes, almost 50% of Snail targets showed an unanticipated activation. The majority of “Snail-activated” genes have enhancer elements cobound by Twist and are expressed in the mesoderm at the stages of Snail occupancy. Snail can potentiate Twist-mediated enhancer activation in vitro and is essential for enhancer activity in vivo. Using a machine learning approach, we show that differentially enriched motifs are sufficient to predict Snail's regulatory response. In silico mutagenesis revealed a likely causative motif, which we demonstrate is essential for enhancer activation. Taken together, these data indicate that Snail can potentiate enhancer activation by collaborating with different activators, providing a new mechanism by which Snail regulates development. Cold Spring Harbor Laboratory Press 2014-01-15 /pmc/articles/PMC3909790/ /pubmed/24402316 http://dx.doi.org/10.1101/gad.230953.113 Text en © 2014 Rembold et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research Paper
Rembold, Martina
Ciglar, Lucia
Yáñez-Cuna, J. Omar
Zinzen, Robert P.
Girardot, Charles
Jain, Ankit
Welte, Michael A.
Stark, Alexander
Leptin, Maria
Furlong, Eileen E.M.
A conserved role for Snail as a potentiator of active transcription
title A conserved role for Snail as a potentiator of active transcription
title_full A conserved role for Snail as a potentiator of active transcription
title_fullStr A conserved role for Snail as a potentiator of active transcription
title_full_unstemmed A conserved role for Snail as a potentiator of active transcription
title_short A conserved role for Snail as a potentiator of active transcription
title_sort conserved role for snail as a potentiator of active transcription
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909790/
https://www.ncbi.nlm.nih.gov/pubmed/24402316
http://dx.doi.org/10.1101/gad.230953.113
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