# Mechanisms and functions of repressive chromatin structure in quiescent cells.

> **NIH NIH K99** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $100,000

## Abstract

Project Summary
 The conformation of chromatin is a primary mechanism by which the cell regulates DNA-templated
processes. Consistent with this broad role, aberrations in the enzymes and structural components responsible
for controlling chromatin dynamics have been linked to an extensive range of human diseases, including the
majority of cancers and an increasing number of genetic and developmental disorders. Recent technological
advancements have increased our knowledge of how the positions of nucleosomes on DNA are regulated and
how chromatin forms large three-dimensional (3D) loops called chromatin domains. 3D chromatin structure is
hypothesized to be capable of both promoting and inhibiting transcription depending on context. However,
understanding the mechanisms and functions of these types of chromatin structures has been difficult due to
the low resolution of current methods, which have made it almost impossible to determine chromatin structure
within cells at scales necessary to determine its relationship to the expression of single-genes. As a result, the
long-held hypothesis that 3D chromatin structure at this level regulates transcription has been largely untested
in a physiological context. To examine 3D chromatin structure in cells in which it is expected to function
extensively, the candidate has implemented a genomics method capable of mapping 3D chromatin structure
genome-wide at unprecedented single-nucleosome 150 base pair resolution in quiescent S. cerevisiae.
Quiescent yeast bear conserved hallmarks of quiescent cells, in particular widespread transcriptional
repression and chromatin condensation, which make them an excellent model for determining the mechanisms
by which 3D chromatin structure represses transcription. Preliminary results have led to the hypothesis that in
quiescent cells, the condensin complex represses transcription by inducing quiescence-specific 3D chromatin
structures. Aim 1 of this proposal will determine how condensin is targeted to form chromatin domains during
quiescence using genomics, microscopy, and a single-molecule magnetic tweezer assay. Aim 2 will examine
the conformation of chromatin within domains to determine if it is folded into 3D structure at a smaller scale
and investigate whether chromatin structure at this scale is the mechanism by which transcription is repressed
during quiescence. The mentored component of this work will be completed under the sponsorship of Dr.
Toshio Tsukiyama, an expert in the chromatin field, at one of the premier institutes for basic science and
cancer research, the Fred Hutchinson Cancer Research Center. The candidate will also be trained in single-
molecule biochemical assays under the supervision of Dr. Sue Biggins, and will expand her proficiency in
bioinformatics through coursework and independent study. This research and training will provide the
candidate with an exciting model system and the skills necessary for a successful independent career.

## Key facts

- **NIH application ID:** 10002245
- **Project number:** 5K99GM134150-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Sarah Grace Swygert
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $100,000
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002245

## Citation

> US National Institutes of Health, RePORTER application 10002245, Mechanisms and functions of repressive chromatin structure in quiescent cells. (5K99GM134150-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10002245. Licensed CC0.

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