Reduced chromatin accessibility correlates with resistance to Notch activation

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  • Jelle van den Ameele
  • Krautz, Robert
  • Seth W. Cheetham
  • Alex P.A. Donovan
  • Oriol Llorà-Batlle
  • Rebecca Yakob
  • Andrea H. Brand
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.
OriginalsprogEngelsk
Artikelnummer2210
TidsskriftNature Communications
Vol/bind13
Udgave nummer1
Antal sider10
ISSN2041-1723
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We thank C.M. Davidson for technical assistance; G. Del Sal, R. Kageyama, F. Polleux, and P. Vanderhaeghen for plasmids; P. Seale for antibodies. We thank the core staff at the Gurdon Institute: K. Harnish (NGS Core facility), C. Bradshaw (Bioinformatics Core), the animal facility and media kitchen. We thank L. Tiberi and P. Vanderhaeghen for help with in utero electroporation, L. Aloia, and P.F. Chinnery for discussion and/or comments on the manuscript and members of the Brand lab for discussions throughout the course of this work and comments on the manuscript. This work was funded by Wellcome Trust Senior Investigator Award (103792/Z/14/Z) and Royal Society Darwin Trust Research Professorship (RP150061) to A.H.B., Wellcome Trust Postdoctoral Training Fellowship for Clinicians (105839/Z/14/Z) to J.v.d.A. and Herchel Smith Research Studentship to S.W.C. A.H.B. acknowledges core funding to the Gurdon Institute from the Wellcome Trust (203144/A/16/Z) and CRUK (C6946/A24843).

Publisher Copyright:
© 2022, The Author(s).

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