TY  - JOUR
AU  - Feng, Weijun
AU  - Kawauchi, Daisuke
AU  - Körkel-Qu, Huiqin
AU  - Deng, Huan
AU  - Serger, Elisabeth
AU  - Sieber, Laura
AU  - Lieberman, Jenna Ariel
AU  - Jimeno-González, Silvia
AU  - Lambo, Sander
AU  - Hanna, Bola
AU  - Harim, Yassin
AU  - Jansen, Malin
AU  - Neuerburg, Anna
AU  - Friesen, Olga
AU  - Zuckermann, Marc
AU  - Rajendran, Vijayanad
AU  - Gronych, Jan
AU  - Ayrault, Olivier
AU  - Korshunov, Andrey
AU  - Jones, David
AU  - Kool, Marcel
AU  - Northcott, Paul A
AU  - Lichter, Peter
AU  - Cortés-Ledesma, Felipe
AU  - Pfister, Stefan
AU  - Liu, Haikun
TI  - Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme.
JO  - Nature Communications
VL  - 8
SN  - 2041-1723
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2017-00892
SP  - 14758
PY  - 2017
N1  - DKFZ-ZMBH Alliance
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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28317875
C2  - pmc:PMC5364396
DO  - DOI:10.1038/ncomms14758
UR  - https://inrepo02.dkfz.de/record/120463
ER  -