PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Nechiporuk, T.* ; McGann, J.* ; Mullendorff, K.* ; Hsieh, J.* ; Wurst, W. ; Floß, T. ; Mandel, G.*

The REST remodeling complex protects genomic integrity during embryonic neurogenesis.

eLife 5:e09584 (2016)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The timely transition from neural progenitor to post-mitotic neuron requires down-regulation and loss of the neuronal transcriptional repressor, REST. Here, we have used mice containing a gene trap in the Rest gene, eliminating transcription from all coding exons, to remove REST prematurely from neural progenitors. We find that catastrophic DNA damage occurs during S-phase of the cell cycle, with long-term consequences including abnormal chromosome separation, apoptosis, and smaller brains. Persistent effects are evident by latent appearance of proneural glioblastoma in adult mice deleted additionally for the tumor suppressor p53 protein (p53). A previous line of mice deleted for REST in progenitors by conventional gene targeting does not exhibit these phenotypes, likely due to a remaining C-terminal peptide that still binds chromatin and recruits co-repressors. Our results suggest that REST-mediated chromatin remodeling is required in neural progenitors for proper S-phase dynamics, as part of its well-established role in repressing neuronal genes until terminal differentiation.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Altmetric
8.303
1.230
36
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Rest Complex ; Developmental Biology ; Genomic Instability ; Knockout Animals ; Mouse ; Neurogenesis ; Repression ; Stem Cells ; Transcription Factors
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 5, Heft: , Seiten: , Artikelnummer: e09584 Supplement: ,
Verlag eLife Sciences Publications
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
PubMed ID 26745185
DOI 10.7554/eLife.09584
WOS ID WOS:000368225700001
Erfassungsdatum 2016-01-11
[➜Korrektur melden]