Reduced chromatin accessibility correlates with resistance to Notch activation.
Donovan, Alex P A
MetadataShow full item record
van den Ameele, J., Krautz, R., Cheetham, S. W., Donovan, A. P. A., 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
Funder: Royal Society
Funder: Herchel Smith Fund
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.
Chromatin, Animals, Mice, Signal Transduction, Cell Differentiation, Receptors, Notch, Neural Stem Cells
Wellcome Trust (103792/Z/14/Z, 105839/Z/14/Z, 103792, 203144/A/16/Z, 105839)
External DOI: https://doi.org/10.1038/s41467-022-29834-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337526
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/