RT Journal Article
T1 Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme.
A1 Feng, Weijun
A1 Kawauchi, Daisuke
A1 Körkel-Qu, Huiqin
A1 Deng, Huan
A1 Serger, Elisabeth
A1 Sieber, Laura
A1 Lieberman, Jenna Ariel
A1 Jimeno-González, Silvia
A1 Lambo, Sander
A1 Hanna, Bola S
A1 Harim, Yassin
A1 Jansen, Malin
A1 Neuerburg, Anna
A1 Friesen, Olga
A1 Zuckermann, Marc
A1 Rajendran, Vijayanad
A1 Gronych, Jan
A1 Ayrault, Olivier
A1 Korshunov, Andrey
A1 Jones, David T W
A1 Kool, Marcel
A1 Northcott, Paul A
A1 Lichter, Peter
A1 Cortés-Ledesma, Felipe
A1 Pfister, Stefan M
A1 Liu, Hai-Kun
AB 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.
YR 2017
FD 2017-03-20
LK http://hdl.handle.net/10668/10974
UL http://hdl.handle.net/10668/10974
LA en
DS RISalud
RD Apr 6, 2025