Fueyo, Raquel, Iacobucci, Simona, Pappa, Stella, Estaras, Conchi ORCID: 0000-0002-2600-5841, Lois, Sergio, Vicioso-Mantis, Marta, Navarro, Claudia, Cruz-Molina, Sara, Carlos Reyes, Jose, Rada-Iglesias, Alvaro, de la Cruz, Xavier and Martinez-Balbas, Marian A. (2018). Lineage specific transcription factors and epigenetic regulators mediate TGF beta-dependent enhancer activation. Nucleic Acids Res., 46 (7). S. 3351 - 3366. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

Full text not available from this repository.

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 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fueyo, RaquelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iacobucci, SimonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pappa, StellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Estaras, ConchiUNSPECIFIEDorcid.org/0000-0002-2600-5841UNSPECIFIED
Lois, SergioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vicioso-Mantis, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Navarro, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cruz-Molina, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carlos Reyes, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rada-Iglesias, AlvaroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de la Cruz, XavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Balbas, Marian A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-189143
DOI: 10.1093/nar/gky093
Journal or Publication Title: Nucleic Acids Res.
Volume: 46
Number: 7
Page Range: S. 3351 - 3366
Date: 2018
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1362-4962
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GROWTH-FACTOR-BETA; NEURAL STEM-CELLS; DEVELOPING SPINAL-CORD; RNA-POLYMERASE-II; GENE-EXPRESSION; IN-VITRO; CORTICAL NEUROGENESIS; PRONEURAL GENES; CHROMATIN; JMJD3Multiple languages
Biochemistry & Molecular BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18914

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item