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@ARTICLE{Huang:300226,
author = {Z. Huang and C. He and G. Wang and M. Zhu and X. Tong and
Y. Feng and C. Zhang and S. Dong and Y. Harim$^*$ and H.
Liu$^*$ and W. Zhou and F. Lan and W. Feng},
title = {{M}utation of {CHD}7 impairs the output of neuroepithelium
transition that is reversed by the inhibition of {EZH}2.},
journal = {Molecular psychiatry},
volume = {30},
number = {9},
issn = {1359-4184},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-00688},
pages = {4094-4109},
year = {2025},
note = {DKFZ-ZMBH Alliance /2025 Sep;30(9):4094-4109},
abstract = {Haploinsufficiency of CHD7 (Chromo-Helicase-DNA binding
protein 7) causes a severe congenital disease CHARGE
syndrome. Brain anomaly such as microcephaly and olfactory
bulb agenesis seen in CHARGE patients have not been mimicked
in previous animal models. Here, we uncover an indispensable
function of CHD7 in the neuroepithelium (NE) but not in the
neural stem cells (NSCs) after NE transition. Loss of Chd7
in mouse NE resulted in CHARGE-like brain anomalies due to
reduced proliferation and differentiation of neural stem and
progenitor cells, which were recapitulated in CHD7 KO human
forebrain organoids. Mechanistically, we find that CHD7
activates neural transcription factors by removing the
repressive histone mark H3K27me3 and promoting chromatin
accessibility. Importantly, neurodevelopmental defects
caused by CHD7 loss in human brain organoids and mice were
ameliorated by the inhibition of H3K27me3 methyltransferase
EZH2. Altogether, by implementing appropriate experimental
models, we uncover the pathogenesis of CHD7-associated
neurodevelopmental diseases, and identify a potential
therapeutic opportunity for CHARGE syndrome.},
cin = {A240},
ddc = {610},
cid = {I:(DE-He78)A240-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40164694},
doi = {10.1038/s41380-025-02990-6},
url = {https://inrepo02.dkfz.de/record/300226},
}