Reduced chromatin accessibility correlates with resistance to Notch activation
Authors
Cheetham, Seth W
Donovan, Alex PA
Brand, Andrea H
Publication Date
2022-04-25Journal Title
Nature Communications
Publisher
Nature Publishing Group UK
Volume
13
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
van den Ameele, J., Krautz, R., Cheetham, S. W., Donovan, A. P., Llorà-Batlle, O., Yakob, R., & Brand, A. H. (2022). Reduced chromatin accessibility correlates with resistance to Notch activation. Nature Communications, 13 (1) https://doi.org/10.1038/s41467-022-29834-z
Description
Funder: Royal Society; doi: https://doi.org/10.13039/501100000288
Funder: Herchel Smith Fund
Abstract
Abstract: The Notch signalling pathway is a master regulator of cell fate transitions in development and disease. In the brain, Notch promotes neural stem cell (NSC) proliferation, regulates neuronal migration and maturation and can act as an oncogene or tumour suppressor. How NOTCH and its transcription factor RBPJ activate distinct gene regulatory networks in closely related cell types in vivo remains to be determined. Here we use Targeted DamID (TaDa), requiring only thousands of cells, to identify NOTCH and RBPJ binding in NSCs and their progeny in the mouse embryonic cerebral cortex in vivo. We find that NOTCH and RBPJ associate with a broad network of NSC genes. Repression of NSC-specific Notch target genes in intermediate progenitors and neurons correlates with decreased chromatin accessibility, suggesting that chromatin compaction may contribute to restricting NOTCH-mediated transactivation.
Keywords
Article, /631/136/142, /631/136/368, /45/100, /45/22, /45/23, /64/60, /14/19, /13/51, article
Sponsorship
Wellcome Trust (Wellcome) (103792, 105839)
Identifiers
s41467-022-29834-z, 29834
External DOI: https://doi.org/10.1038/s41467-022-29834-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336421
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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