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Título: | Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation |
Autor: | Fueyo, Raquel CSIC ORCID; Iacobucci, Simona CSIC ; Pappa, Stella CSIC ; Estarás, Conchi CSIC ORCID; Lois, Sergio; Vicioso Mantis, Marta CSIC ORCID ; Navarro, Claudia CSIC ORCID; Cruz-Molina, Sara; Reyes, José C. CSIC ORCID ; Rada-Iglesias, Alvaro CSIC ORCID; Cruz, Xavier de la CSIC ORCID; Martínez-Balbás, Marian CSIC ORCID | Fecha de publicación: | 20-abr-2018 | Editor: | Oxford University Press | Citación: | Nucleic Acids Research 46(7): 3351–3365 (2018) | Resumen: | 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. | Versión del editor: | https://doi.org/10.1093/nar/gky093 | URI: | http://hdl.handle.net/10261/180513 | DOI: | 10.1093/nar/gky093 | ISSN: | 0305-1048 | E-ISSN: | 1362-4962 |
Aparece en las colecciones: | (CNB) Artículos (IBMB) Artículos (CABIMER) Artículos |
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Lineage specific_Fueyo.pdf | 4,35 MB | Adobe PDF | Visualizar/Abrir |
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