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Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation

During neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to whic...

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Autores principales: Fueyo, Raquel, Iacobucci, Simona, Pappa, Stella, Estarás, Conchi, Lois, Sergio, Vicioso-Mantis, Marta, Navarro, Claudia, Cruz-Molina, Sara, Reyes, José Carlos, Rada-Iglesias, Álvaro, de la Cruz, Xavier, Martínez-Balbás, Marian A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909450/
https://www.ncbi.nlm.nih.gov/pubmed/29438503
http://dx.doi.org/10.1093/nar/gky093
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author Fueyo, Raquel
Iacobucci, Simona
Pappa, Stella
Estarás, Conchi
Lois, Sergio
Vicioso-Mantis, Marta
Navarro, Claudia
Cruz-Molina, Sara
Reyes, José Carlos
Rada-Iglesias, Álvaro
de la Cruz, Xavier
Martínez-Balbás, Marian A
author_facet Fueyo, Raquel
Iacobucci, Simona
Pappa, Stella
Estarás, Conchi
Lois, Sergio
Vicioso-Mantis, Marta
Navarro, Claudia
Cruz-Molina, Sara
Reyes, José Carlos
Rada-Iglesias, Álvaro
de la Cruz, Xavier
Martínez-Balbás, Marian A
author_sort Fueyo, Raquel
collection PubMed
description During neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to which extent chromatin modifiers contribute to enhancer activity is starting to be uncovered. Here, we take advantage of neural stem cells as a model to unravel the mechanisms underlying neural enhancer activation in response to the TGFβ signaling. Genome-wide experiments demonstrate that the proneural factor ASCL1 assists SMAD3 in the binding to a subset of enhancers. Once located at the enhancers, SMAD3 recruits the histone demethylase JMJD3 and the remodeling factor CHD8, creating the appropriate chromatin landscape to allow enhancer transcription and posterior gene activation. Finally, to analyze the phenotypical traits owed to cis-regulatory regions, we use CRISPR–Cas9 technology to demonstrate that the TGFβ-responsive Neurog2 enhancer is essential for proper neuronal polarization.
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spelling pubmed-59094502018-04-24 Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation Fueyo, Raquel Iacobucci, Simona Pappa, Stella Estarás, Conchi Lois, Sergio Vicioso-Mantis, Marta Navarro, Claudia Cruz-Molina, Sara Reyes, José Carlos Rada-Iglesias, Álvaro de la Cruz, Xavier Martínez-Balbás, Marian A Nucleic Acids Res Gene regulation, Chromatin and Epigenetics During neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to which extent chromatin modifiers contribute to enhancer activity is starting to be uncovered. Here, we take advantage of neural stem cells as a model to unravel the mechanisms underlying neural enhancer activation in response to the TGFβ signaling. Genome-wide experiments demonstrate that the proneural factor ASCL1 assists SMAD3 in the binding to a subset of enhancers. Once located at the enhancers, SMAD3 recruits the histone demethylase JMJD3 and the remodeling factor CHD8, creating the appropriate chromatin landscape to allow enhancer transcription and posterior gene activation. Finally, to analyze the phenotypical traits owed to cis-regulatory regions, we use CRISPR–Cas9 technology to demonstrate that the TGFβ-responsive Neurog2 enhancer is essential for proper neuronal polarization. Oxford University Press 2018-04-20 2018-02-09 /pmc/articles/PMC5909450/ /pubmed/29438503 http://dx.doi.org/10.1093/nar/gky093 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Fueyo, Raquel
Iacobucci, Simona
Pappa, Stella
Estarás, Conchi
Lois, Sergio
Vicioso-Mantis, Marta
Navarro, Claudia
Cruz-Molina, Sara
Reyes, José Carlos
Rada-Iglesias, Álvaro
de la Cruz, Xavier
Martínez-Balbás, Marian A
Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_full Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_fullStr Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_full_unstemmed Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_short Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_sort lineage specific transcription factors and epigenetic regulators mediate tgfβ-dependent enhancer activation
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909450/
https://www.ncbi.nlm.nih.gov/pubmed/29438503
http://dx.doi.org/10.1093/nar/gky093
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