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Song, Hye Min
유전체 항상성 연구단
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Haematopoietic stem cell-dependent Notch transcription is mediated by p53 through the Histone chaperone Supt16h

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Title
Haematopoietic stem cell-dependent Notch transcription is mediated by p53 through the Histone chaperone Supt16h
Author(s)
Sophia G. Espanola; Hyemin Song; Eunjin Ryu; Aditya Saxena; Eun-Sun Kim; Jennifer E. Manegold; Chanond A. Nasamran; Debashis Sahoo; Chang-Kyu Oh; Cara Bickers; Unbeom Shin; Stephanie Grainger; Yong Hwan Park; Lauren Pandolfo; Mi-Sun Kang; Sukhyun Kang; Kyungjae Myung; Kimberly L. Cooper; Deborah Yelon; David Traver; Yoonsung Lee
Subject
RNA-POLYMERASE-II, ; DEVELOPMENTAL REGULATORS, ; QUALITY-CONTROL, ; POLYCOMB, ; FATE, ; FACT, ; GENE, ; CHROMATIN, ; SPECIFICATION, ; ELONGATION
Publication Date
2020-12
Journal
NATURE CELL BIOLOGY, v.22, pp.1411 - 1422
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. 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
URI
https://pr.ibs.re.kr/handle/8788114/7512
DOI
10.1038/s41556-020-00604-7
ISSN
1465-7392
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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