# Mechanisms and functions of chromatin regulation for cell-cycle control

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $362,075

## Abstract

Project Summary/Abstract
which cell-cycle is regulated, with an emphasis on mechanisms of cell quiescence through chromatin
regulation. Eukaryotic cells, from single cell organisms to humans, spend most of their time in
quiescence, in which cell exit mitotic cell-cycle in a reversible fashion for long-term survival. Proper
control of entry into, maintenance of, and exit from quiescence is essential for cell survival, normal
development of organisms, stem cell maintenance and prevention of cancer. However, molecular
mechanisms underlying quiescence remains largely unknown. Chromatin regulation plays integral roles
in a wide variety of DNA-dependent processes, including transcription, DNA replication, DNA repair,
recombination, kinetochore formation, and DNA damage checkpoint response. Therefore, elucidating
the mechanisms of chromatin regulation is a necessary prerequisite for understanding how these
essential processes are controlled. One of the major challenges in studying chromatin regulation is to
elucidate how chromatin regulation affects such a wide variety of processes in the context of important
biological contexts, such as cell cycle control and cell differentiation. This is a particularly important
challenge, because it was recently determined that mutations in chromatin regulators represent one
major class of so called cancer driver mutations, and how these mutations accerelate cancer
development remains unknown. Therefore, elucidating the mechanisms of chromatin regulation impacts
not only the researchers who study fundamental principle of DNA-dependent processes, but also those
who investigate cancer biology and mechanisms of genome stability maintenance.
 It was recently found that the budding yeast S. cerevisiae can enter quiescent state that share
many properties with mammalian quiescence, and a method to purify the quiescent cell was developed.
Taking advantage of this system, we have found strong evidence that degradation of specific sets of
mRNA is essential for quiescence entry. This strongly suggest the presence of currently unknown
mechanism to regulate quiescence entry. We have also found that the high-order structure of chromatin
is regulated in quiescence in a way distinct from exponentially growing cells. First, we found that
condensin, a highly conserved regulator of chromatin higher-order structure, globally re-localizes during
quiescence entry and play key roles in chromatin domain structure in quiescent cells. Secondly, we
found that nucleosome arrays are folded into different fashion in quiescent cells. We will take
advantage of these recent findings and determine the molecular basis for these observations, which will
address a significant gap in our current knowledge about mechanisms underlying quiescence and
higher-order chromatin structure.

## Key facts

- **NIH application ID:** 10015288
- **Project number:** 5R01GM111428-06
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** TOSHIO TSUKIYAMA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,075
- **Award type:** 5
- **Project period:** 2015-05-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10015288

## Citation

> US National Institutes of Health, RePORTER application 10015288, Mechanisms and functions of chromatin regulation for cell-cycle control (5R01GM111428-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10015288. Licensed CC0.

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