期刊
NUCLEIC ACIDS RESEARCH
卷 46, 期 7, 页码 3351-3365出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky093
关键词
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资金
- Spanish Ministry of Education and Science [BFU2015-69248-P, BFU20012-34261, BFU2015-69248]
- Fundacio La Marato de TV3 [090210]
- Jerome Lejeune Fondation
- FPU fellowship from the Company of Biologists
- Company of Biologists
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 TGF beta 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 cisregulatory regions, we use CRISPR-Cas9 technology to demonstrate that the TGF beta-responsive Neurog2 enhancer is essential for proper neuronal polarization.
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