Eintrag weiter verarbeiten
Verfügbar über Online-Ressource

Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme

Gespeichert in:

Veröffentlicht in: Nature Communications 8(2017) Artikel-Nummer 14758, 14 Seiten
Personen und Körperschaften: Feng, Weijun (VerfasserIn), Kawauchi, Daisuke (VerfasserIn), Hanna, Bola (VerfasserIn), Korshunov, Andrey (VerfasserIn), Jones, David T. W. (VerfasserIn), Kool, Marcel (VerfasserIn), Lichter, Peter (VerfasserIn), Pfister, Stefan (VerfasserIn), Liu, Hai-Kun (VerfasserIn)
Titel: Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme/ Weijun Feng, Daisuke Kawauchi, Huiqin Körkel-Qu, Huan Deng, Elisabeth Serger, Laura Sieber, Jenna Ariel Lieberman, Silvia Jimeno-González, Sander Lambo, Bola S. Hanna, Yassin Harim, Malin Jansen, Anna Neuerburg, Olga Friesen, Marc Zuckermann, Vijayanad Rajendran, Jan Gronych, Olivier Ayrault, Andrey Korshunov, David T.W. Jones, Marcel Kool, Paul A. Northcott, Peter Lichter, Felipe Cortés-Ledesma, Stefan M. Pfister & Hai-Kun Liu
Format: E-Book-Kapitel
Sprache: Englisch
veröffentlicht:
20 Mar 2017
Gesamtaufnahme: : Nature Communications, 8(2017) Artikel-Nummer 14758, 14 Seiten
, volume:8
Quelle: Verbunddaten SWB
Lizenzfreie Online-Ressourcen
Details
Zusammenfassung: Mutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), frequently associated with CHARGE syndrome, is indispensable for normal cerebellar development. Genetic inactivation of Chd7 in cerebellar granule neuron progenitors leads to cerebellar hypoplasia in mice, due to the impairment of granule neuron differentiation, induction of apoptosis and abnormal localization of Purkinje cells, which closely recapitulates known clinical features in the cerebella of CHARGE patients. Combinatory molecular analyses reveal that Chd7 is required for the maintenance of open chromatin and thus activation of genes essential for granule neuron differentiation. We further demonstrate that both Chd7 and Top2b are necessary for the transcription of a set of long neuronal genes in cerebellar granule neurons. Altogether, our comprehensive analyses reveal a mechanism with chromatin remodellers governing brain development via controlling a core transcriptional programme for cell-specific differentiation.
Beschreibung: Gesehen am 30.08.2019
Umfang: 14
ISSN: 2041-1723
DOI: 10.1038/ncomms14758