Fueyo, RaquelIacobucci, SimonaPappa, StellaEstarás, ConchiLois, SergioVicioso-Mantis, MartaNavarro, ClaudiaCruz-Molina, SaraReyes, José CarlosRada-Iglesias, Álvarode la Cruz, XavierMartínez-Balbás, Marian A2023-01-252023-01-252018http://hdl.handle.net/10668/12125During 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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/AnimalsBasic Helix-Loop-Helix Transcription FactorsCRISPR-Cas SystemsCell LineageCell PolarityDNA-Binding ProteinsEnhancer Elements, GeneticEpigenesis, GeneticJumonji Domain-Containing Histone DemethylasesMiceNerve Tissue ProteinsNeural Stem CellsNeurogenesisPromoter Regions, GeneticSignal TransductionSmad3 ProteinTranscription FactorsTransforming Growth Factor betaresearch article29438503open access10.1093/nar/gky0931362-4962PMC5909450https://academic.oup.com/nar/article-pdf/46/7/3351/24677394/gky093.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909450/pdf