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Baumann, V.* ; Wiesbeck, M.* ; Breunig, C.T.* ; Braun, J.M.* ; Köferle, A.* ; Ninkovic, J. ; Götz, M. ; Stricker, S.H.

Targeted removal of epigenetic barriers during transcriptional reprogramming.

Nat. Commun. 10:2119 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Neural Stem-cells; Dna-methylation; Gene-expression; Sox1; Neurogenesis; Activation; Binding; Differentiation; Precursors; Inhibitor
Sprache
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 2119 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Stem Cell and Neuroscience
PSP-Element(e) G-500800-001
DOI 10.1038/s41467-019-10146-8
WOS ID WOS:000467535100005
PubMed ID 31073172
Erfassungsdatum 2019-05-17
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