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

Jung-Won Lee, Da-Mi Kim, Ju-Won Jang, Tae-Geun Park, Soo-Hyun Song, You-Soub Lee, Xin-Zi Chi, Il Yeong Park, Jin-Won Hyun, Yoshiaki Ito and Suk-Chul Bae ()
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Jung-Won Lee: School of Medicine, and Institute for Tumor Research, Chungbuk National University
Da-Mi Kim: School of Medicine, and Institute for Tumor Research, Chungbuk National University
Ju-Won Jang: School of Medicine, and Institute for Tumor Research, Chungbuk National University
Tae-Geun Park: School of Medicine, and Institute for Tumor Research, Chungbuk National University
Soo-Hyun Song: School of Medicine, and Institute for Tumor Research, Chungbuk National University
You-Soub Lee: School of Medicine, and Institute for Tumor Research, Chungbuk National University
Xin-Zi Chi: School of Medicine, and Institute for Tumor Research, Chungbuk National University
Il Yeong Park: College of Pharmacy, Chungbuk National University
Jin-Won Hyun: School of Medicine, Jeju National University
Yoshiaki Ito: Cancer Science Institute of Singapore, National University of Singapore
Suk-Chul Bae: School of Medicine, and Institute for Tumor Research, Chungbuk National University

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09810-w

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