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@ARTICLE{Reddy:176932,
author = {N. C. Reddy and S. P. Majidi and L. Kong and M. Nemera and
C. J. Ferguson and M. Moore and T. M. Goncalves and H.-K.
Liu$^*$ and J. A. J. Fitzpatrick and G. Zhao and T. Yamada
and A. Bonni and H. W. Gabel},
title = {{CHARGE} syndrome protein {CHD}7 regulates epigenomic
activation of enhancers in granule cell precursors and
gyrification of the cerebellum.},
journal = {Nature Communications},
volume = {12},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2021-02172},
pages = {5702},
year = {2021},
note = {DKFZ-ZMBH Alliance},
abstract = {Regulation of chromatin plays fundamental roles in the
development of the brain. Haploinsufficiency of the
chromatin remodeling enzyme CHD7 causes CHARGE syndrome, a
genetic disorder that affects the development of the
cerebellum. However, how CHD7 controls chromatin states in
the cerebellum remains incompletely understood. Using
conditional knockout of CHD7 in granule cell precursors in
the mouse cerebellum, we find that CHD7 robustly promotes
chromatin accessibility, active histone modifications, and
RNA polymerase recruitment at enhancers. In vivo profiling
of genome architecture reveals that CHD7 concordantly
regulates epigenomic modifications associated with enhancer
activation and gene expression of topologically-interacting
genes. Genome and gene ontology studies show that
CHD7-regulated enhancers are associated with genes that
control brain tissue morphogenesis. Accordingly, conditional
knockout of CHD7 triggers a striking phenotype of cerebellar
polymicrogyria, which we have also found in a case of CHARGE
syndrome. Finally, we uncover a CHD7-dependent switch in the
preferred orientation of granule cell precursor division in
the developing cerebellum, providing a potential cellular
basis for the cerebellar polymicrogyria phenotype upon loss
of CHD7. Collectively, our findings define epigenomic
regulation by CHD7 in granule cell precursors and identify
abnormal cerebellar patterning upon CHD7 depletion, with
potential implications for our understanding of CHARGE
syndrome.},
cin = {A240},
ddc = {500},
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:34588434},
doi = {10.1038/s41467-021-25846-3},
url = {https://inrepo02.dkfz.de/record/176932},
}