Journal Article

DKFZ-2017-00892

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme.

Feng, W. (First author)DKFZ* ; Kawauchi, D. (First author)DKFZ* ; Körkel-Qu, H.DKFZ* ; Deng, H.DKFZ* ; Serger, E.DKFZ* ; Sieber, L.DKFZ* ; Lieberman, J. A. ; Jimeno-González, S. ; Lambo, S.DKFZ* ; Hanna, B.DKFZ* ; Harim, Y.DKFZ* ; Jansen, M.DKFZ* ; Neuerburg, A.DKFZ* ; Friesen, O.DKFZ* ; Zuckermann, M.DKFZ* ; Rajendran, V.DKFZ* ; Gronych, J.DKFZ* ; Ayrault, O. ; Korshunov, A.DKFZ* ; Jones, D.DKFZ* ; Kool, M.DKFZ* ; Northcott, P. A. ; Lichter, P.DKFZ* ; Cortés-Ledesma, F. ; Pfister, S.DKFZ* ; Liu, H. (Last author)DKFZ*

2017
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/ncomms14758

Abstract: 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.

Note: DKFZ-ZMBH Alliance

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Contributing Institute(s):

1. A240 Molekulare Neurogenetik (A240)
2. B062 Pädiatrische Neuroonkologie (B062)
3. B060 Molekulare Genetik (B060)
4. KKE Neuropathologie (G380)
5. DKTK Heidelberg (L101)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2017

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Database coverage:
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