Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2014
|
Materias: | |
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 |
_version_ | 1782301889271955456 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3909790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT remboldmartina aconservedroleforsnailasapotentiatorofactivetranscription AT ciglarlucia aconservedroleforsnailasapotentiatorofactivetranscription AT yanezcunajomar aconservedroleforsnailasapotentiatorofactivetranscription AT zinzenrobertp aconservedroleforsnailasapotentiatorofactivetranscription AT girardotcharles aconservedroleforsnailasapotentiatorofactivetranscription AT jainankit aconservedroleforsnailasapotentiatorofactivetranscription AT weltemichaela aconservedroleforsnailasapotentiatorofactivetranscription AT starkalexander aconservedroleforsnailasapotentiatorofactivetranscription AT leptinmaria aconservedroleforsnailasapotentiatorofactivetranscription AT furlongeileenem aconservedroleforsnailasapotentiatorofactivetranscription AT remboldmartina conservedroleforsnailasapotentiatorofactivetranscription AT ciglarlucia conservedroleforsnailasapotentiatorofactivetranscription AT yanezcunajomar conservedroleforsnailasapotentiatorofactivetranscription AT zinzenrobertp conservedroleforsnailasapotentiatorofactivetranscription AT girardotcharles conservedroleforsnailasapotentiatorofactivetranscription AT jainankit conservedroleforsnailasapotentiatorofactivetranscription AT weltemichaela conservedroleforsnailasapotentiatorofactivetranscription AT starkalexander conservedroleforsnailasapotentiatorofactivetranscription AT leptinmaria conservedroleforsnailasapotentiatorofactivetranscription AT furlongeileenem conservedroleforsnailasapotentiatorofactivetranscription |