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Targeted removal of epigenetic barriers during transcriptional reprogramming.
Nat. Commun. 10:2119 (2019)
Master transcription factors have the ability to direct and reverse cellular identities, and consequently their genes must be subject to particular transcriptional control. However, it is unclear which molecular processes are responsible for impeding their activation and safeguarding cellular identities. Here we show that the targeting of dCas9-VP64 to the promoter of the master transcription factor Sox1 results in strong transcript and protein up-regulation in neural progenitor cells (NPCs). This gene activation restores lost neuronal differentiation potential, which substantiates the role of Sox1 as a master transcription factor. However, despite efficient transactivator binding, major proportions of progenitor cells are unresponsive to the transactivating stimulus. By combining the transactivation domain with epigenome editing we find that among a series of euchromatic processes, the removal of DNA methylation (by dCas9-Tet1) has the highest potential to increase the proportion of cells activating foreign master transcription factors and thus breaking down cell identity barriers.
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Times Cited
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11.878
2.805
28
34
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Neural Stem-cells; Dna-methylation; Gene-expression; Sox1; Neurogenesis; Activation; Binding; Differentiation; Precursors; Inhibitor
Language
Publication Year
2019
HGF-reported in Year
2019
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 10,
Issue: 1,
Article Number: 2119
Publisher
Nature Publishing Group
Publishing Place
London
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)
POF-Topic(s)
30204 - Cell Programming and Repair
Research field(s)
Stem Cell and Neuroscience
PSP Element(s)
G-500800-001
WOS ID
WOS:000467535100005
PubMed ID
31073172
Erfassungsdatum
2019-05-17