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Title: Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation.
Authors: 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
metadata.dc.subject.mesh: Animals
Basic Helix-Loop-Helix Transcription Factors
CRISPR-Cas Systems
Cell Lineage
Cell Polarity
DNA-Binding Proteins
Enhancer Elements, Genetic
Epigenesis, Genetic
Jumonji Domain-Containing Histone Demethylases
Nerve Tissue Proteins
Neural Stem Cells
Promoter Regions, Genetic
Signal Transduction
Smad3 Protein
Transcription Factors
Transforming Growth Factor beta
Issue Date: 2018
Abstract: 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.
metadata.dc.identifier.doi: 10.1093/nar/gky093
Appears in Collections:Producción 2020

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