# Mechanisms of massive genome reactivation during quiescence exit

> **NIH NIH F32** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $65,310

## Abstract

ABSTRACT
Many cells in our body are alive, but reversibly dormant, in a conserved stage of the cell cycle called quiescence.
Quiescent cells can inhibit DNA-templated processes via the establishment of a repressive chromatin
environment, and it was recently discovered that widespread histone deacetylation is required for quiescence.
How cells overcome this repressive chromatin state for quiescence exit is unknown. The goal of this proposal is
to elucidate fundamental, conserved mechanisms of chromatin regulation of transcription activation and DNA
replication in quiescence exit, an understudied area with broad applications to human health. Intriguingly, I have
uncovered persisting histone acetylation at inactive genes in quiescent cells that correspond to genes induced
immediately during quiescence exit. However, the mechanism underlying this unexpected phenomenon is
undefined. This proposal will shed light on the roles of histone acetylation in poising genes for rapid activation
and will determine the mechanism for how poised promoter architecture is established in quiescent cells.
Downstream of genome reprogramming events during early exit, cells globally reposition nucleosomes. In cycling
cells, it has been shown that nucleosome positioning around DNA replication origins (origin) can strongly
influence origin activity. However, a model system to investigate mechanisms and functions of nucleosome
repositioning around origins in a physiologically relevant context has not been available. Preliminary data from
the lab indicate that nucleosomes reposition substantially around origins during quiescence exit compared to
cycling cells. Specifically, dramatic changes in the width of nucleosome-depleted regions (NDRs) around origins
occur by the first G1 after quiescence exit. Preliminary data suggest that the essential, SWI/SNF family chromatin
remodeling enzyme RSC is responsible for this repositioning and that RSC plays a role in regulating S phase.
Based on these results, I will elucidate the role of RSC and nucleosome positioning in DNA replication as cells
exit quiescence. To determine the conservation of these mechanisms, these models will be tested in human
cells. Cumulatively, this proposal will address outstanding questions on how the genome is reprogrammed for
DNA-templated processes during quiescence exit.

## Key facts

- **NIH application ID:** 9982682
- **Project number:** 5F32GM131554-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Christine E Cucinotta
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-07-23 → 2021-07-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982682

## Citation

> US National Institutes of Health, RePORTER application 9982682, Mechanisms of massive genome reactivation during quiescence exit (5F32GM131554-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9982682. Licensed CC0.

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