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Reduced chromatin accessibility correlates with resistance to Notch activation

Author

Listed:
  • Jelle Ameele

    (University of Cambridge
    University of Cambridge)

  • Robert Krautz

    (University of Cambridge
    University of Copenhagen)

  • Seth W. Cheetham

    (University of Cambridge
    Mater Research Institute-University of Queensland)

  • Alex P. A. Donovan

    (University of Cambridge)

  • Oriol Llorà-Batlle

    (University of Cambridge)

  • Rebecca Yakob

    (University of Cambridge)

  • Andrea H. Brand

    (University of Cambridge)

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.

Suggested Citation

  • Jelle Ameele & Robert Krautz & Seth W. Cheetham & Alex P. A. Donovan & Oriol Llorà-Batlle & Rebecca Yakob & Andrea H. Brand, 2022. "Reduced chromatin accessibility correlates with resistance to Notch activation," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29834-z
    DOI: 10.1038/s41467-022-29834-z
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