| Literature DB >> 33230303 |
Sophia G Espanola1, Hyemin Song1,2, Eunjin Ryu3, Aditya Saxena4, Eun-Sun Kim2, Jennifer E Manegold1, Chanond A Nasamran5, Debashis Sahoo6, Chang-Kyu Oh2, Cara Bickers1, Unbeom Shin3, Stephanie Grainger4, Yong Hwan Park2, Lauren Pandolfo4, Mi-Sun Kang2, Sukhyun Kang2, Kyungjae Myung2,3, Kimberly L Cooper4, Deborah Yelon4, David Traver7, Yoonsung Lee8,9,10.
Abstract
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.Entities:
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Year: 2020 PMID： 33230303 PMCID： PMC8092813 DOI： 10.1038/s41556-020-00604-7
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824