Haematopoietic stem cell-dependent Notch transcription is mediated by p53 through the Histone chaperone Supt16h

Nat Cell Biol. 2020 Dec;22(12):1411-1422. doi: 10.1038/s41556-020-00604-7. Epub 2020 Nov 23.


Haematopoietic stem and progenitor cells (HSPCs) have been the focus of developmental and regenerative studies, yet our understanding of the signalling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the Facilitates chromatin transcription (FACT) complex, is required for HSPC formation. Zebrafish supt16h mutants express reduced levels of Notch-signalling components, genes essential for HSPC development, due to abrogated transcription. Whereas global chromatin accessibility in supt16h mutants is not substantially altered, we observe a specific increase in p53 accessibility, causing an accumulation of p53. We further demonstrate that p53 influences expression of the Polycomb-group protein PHC1, which functions as a transcriptional repressor of Notch genes. Suppression of phc1 or its upstream regulator, p53, rescues the loss of both Notch and HSPC phenotypes in supt16h mutants. Our results highlight a relationship between supt16h, p53 and phc1 to specify HSPCs via modulation of Notch signalling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Developmental
  • Gene Ontology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Mutation
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / growth & development
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism


  • Cell Cycle Proteins
  • Receptors, Notch
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Zebrafish Proteins
  • Polycomb Repressive Complex 1