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Cited by 57Genomics and Chromatin DynamicsChromatin Remodeling and CancerCancer-related Molecular Pathways

RUNX3 regulates cell cycle-dependent chromatin dynamics by functioning as a pioneer factor of the restriction-point

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Lee, Jung-Won, Kim, Da-Mi, Jang, Ju-Won, Park, Tae-Geun, Song, Soo-Hyun, Lee, You-Soub, Chi, Xin-Zi, Park, Il Yeong +3 more·2019·Nature Communications
DOI 10.1038/s41467-019-09810-wPMC PMC6479060

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Abstract

The cellular decision regarding whether to undergo proliferation or death is made at the restriction (R)-point, which is disrupted in nearly all tumors. The identity of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in cell biology. We found that early after mitogenic stimulation, RUNX3 binds to its target loci, where it opens chromatin structure by sequential recruitment of Trithorax group proteins and cell-cycle regulators to drive cells to the R-point. Soon after, RUNX3 closes these loci by recruiting Polycomb repressor complexes, causing the cell to pass through the R-point toward S phase. If the RAS signal is constitutively activated, RUNX3 inhibits cell cycle progression by maintaining R-point-associated genes in an open structure. Our results identify RUNX3 as a pioneer factor for the R-point and reveal the molecular mechanisms by which appropriate chromatin modifiers are selectively recruited to target loci for appropriate R-point decisions.

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Cited by

Sorted by citations

Authors
Lee, J.-W., Kim, D.-M., Jang, J.-W., Park, T.-G., Song, S.-H., Lee, Y.-S., Chi, X.-Z., Park, I. Y., Hyun, J.-W., Ito, Y., & Bae, S.-C.
Affiliations
  • Chungbuk National University (KR)
  • Jeju National University (KR)
  • National University of Singapore (SG)
Corresponding author
Bae, Suk-Chul
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-04-23
Volume
10
Issue
1
Pages
1897-1897
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-09810-w
PMC
PMC6479060
OpenAlex
W2950101086
Cited by
57
References
4
Citations by year
2026: 6 · 2025: 8 · 2024: 4 · 2023: 13 · 2022: 4 · 2021: 9 · 2020: 9 · 2019: 3 · 2018: 1
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation
  • National Research Foundation Singapore
  • Ministry of Science, ICT and Future Planning (NRF-2017R1A4A1014512, 2017R1A4A1014512)
  • Rural Development Administration
  • Korean Foundation for Cancer Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
RUNX3, restriction point, cell cycle regulation, chromatin dynamics, pioneer factors, Trithorax group proteins, Ras signaling, cell proliferation, cell death, mitogen stimulation
MeSH terms
Animals, Butadienes, Chromatin, Drosophila melanogaster, Epithelial Cells, Gene Expression Regulation, Humans, Imidazoles, Nitriles, Piperazines, Histone-Lysine N-Methyltransferase, Pyridines, Signal Transduction, ras Proteins, Sirolimus, RNA, Small Interfering, Chromatin Assembly and Disassembly, Cell Line, Tumor, Protein Kinase Inhibitors, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase 1, MAP Kinase Kinase 4, Cell Proliferation, Core Binding Factor Alpha 3 Subunit, Cyclin-Dependent Kinase 4, Myeloid-Lymphoid Leukemia Protein, HEK293 Cells, TOR Serine-Threonine Kinases, Cell Cycle Checkpoints, Polycomb-Group Proteins

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