RT Journal Article
T1 Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation.
A1 Fueyo, Raquel
A1 Iacobucci, Simona
A1 Pappa, Stella
A1 Estarás, Conchi
A1 Lois, Sergio
A1 Vicioso-Mantis, Marta
A1 Navarro, Claudia
A1 Cruz-Molina, Sara
A1 Reyes, José Carlos
A1 Rada-Iglesias, Álvaro
A1 de la Cruz, Xavier
A1 Martínez-Balbás, Marian A
AB 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.
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12125
UL http://hdl.handle.net/10668/12125
LA en
DS RISalud
RD Apr 6, 2025