Reduced chromatin accessibility correlates with resistance to Notch activation

• Published in: Nature communications Vol. 13; no. 1; p. 2210
• Main Authors: van den Ameele, Jelle, Krautz, Robert, Cheetham, Seth W, Donovan, Alex P A, Llorà-Batlle, Oriol, Yakob, Rebecca, Brand, Andrea H
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 25.04.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Accessibility; Animals; Brain stem; Cell Differentiation - physiology; Cell fate; Cell migration; Cerebral cortex; Chromatin; Chromatin remodeling; Embryos; Gene expression; Gene silencing; Genes; In vivo methods and tests; Mice; Neural stem cells; Neural Stem Cells - metabolism; Occupancy; Progenitor cells; Progeny; Receptors, Notch - metabolism; Signal Transduction; Signaling; Stem cells; Transcription factors; Tumor suppressor genes; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29834-z

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.