# Chromatin Dynamics in the Cell Cycle

> **NIH NIH F32** · STANFORD UNIVERSITY · 2020 · $17,327

## Abstract

Project Summary/Abstract
The ability of cells to robustly enter and exit quiescence is essential for tissue homeostasis, and defects in the
transition between proliferation and quiescence lead to diseases of excess proliferation (cancer) or cell loss
(aging and degeneration). Critical to this transition are gene expression changes regulated by well understood
signaling pathways. In addition to transcriptional changes, chromatin modification and accessibility is regulated
between quiescent and proliferating cells, and the functions of chromatin modifiers have been shown to disrupt
these transitions. However, the mechanisms by which chromatin affects the ability of cells to transition between
quiescence and proliferation are unknown.
The goal of this proposal is to characterize global and gene-specific chromatin modification and accessibility
changes, and define how chromatin regulation affects the ability of cells to transition in and out of quiescence.
The central hypothesis is that distinct chromatin modifications regulate the entry, exit, and maintenance of
quiescence through control of both chromatin accessibility and site-specific transcriptional control of critical cell
cycle genes. This hypothesis will be tested in three specific aims:
(1) Define the functional role of global changes in chromatin modifications in proliferating and quiescent cells.
(2) Identify and induce site-specific chromatin modification changes at the promoters of critical cell cycle
regulated genes.
(3) Determine changes in chromatin accessibility in quiescent and proliferating cells.
Global and site-specific chromatin modifications changes will be identified in quiescent and proliferating human
epithelial cells. The role of these changes in cell cycle regulation will be determined by disrupting the chromatin
regulators responsible for the deposition and removal of the modifications of interest, and using time lapse
microscopy to image live-cell sensors for activities critical to cell cycle progression. This quantitative method will
identify aspects of the cell cycle, which are perturbed by changes in chromatin modification, including probability
of quiescence and time to cell cycle re-entry. Moreover, changes in chromatin accessibility in this critical
transition will be identified, and the role of modifications in regulating chromatin accessibility will be evaluated.
This work will contribute to the field by defining a novel pathway, chromatin dynamics, which functions to regulate
cell cycle entry and exit. Furthermore, the proposed work will advance the understanding of the mechanisms by
which chromatin modifiers control the establishment and maintenance of chromatin marks. Finally, the proposed
work will offer new targets for therapeutic treatment of diseases of tissue homeostasis, including cancer.

## Key facts

- **NIH application ID:** 10228361
- **Project number:** 3F32GM125246-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lindsey Renee Pack
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $17,327
- **Award type:** 3
- **Project period:** 2017-09-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228361

## Citation

> US National Institutes of Health, RePORTER application 10228361, Chromatin Dynamics in the Cell Cycle (3F32GM125246-03S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10228361. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*