# Molecular mechanisms and functions of global chromatin control

> **NIH NIH R35** · FRED HUTCHINSON CANCER CENTER · 2022 · $740,592

## Abstract

Project Summary/Abstract
The long term goal of the proposed study is to determine, at the molecular level, mechanisms and
functions of chromatin regulation at a global level. Chromatin regulation profoundly affects a wide
variety of DNA-dependent processes, including transcription, DNA replication, recombination, DNA
repair, and DNA damage 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 the chromatin field is to elucidate how chromatin is globally reprogrammed during
processes like cell fate determination, development and cell-cycle control. 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, yet how these mutations drive cancer
remains unknown. Therefore, elucidating the mechanisms of chromatin regulation impacts not only the
researchers who study fundamental principles of DNA-dependent processes, but also cancer biologists.
 We have previously elucidated how chromatin regulation affects transcription, DNA replication,
S phase checkpoint and recombination using budding yeast as a model organism. Like most studies in
the field, we did our work during the mitotic cell-cycle. However, yeast cells in the wild, like other
eukaryotic cells, spend most of their time in quiescence. Quiescence is associated with massive
chromatin reprogramming for global condensation. Because the vast majority of work on chromatin
regulation has been done during mitotic cell-cycle, we have little idea of how chromatin is regulated
during the time cells spend most of their time. In order to understand the whole picture of chromatin
regulation in vivo, it is essential to understand mechanisms and functions of chromatin regulation during
quiescence. In the next funding period, we will ask the following questions in quiescent state: 1) How is
chromatin globally reprogrammed by ATP-dependent chromatin remodeling factors? 2) How are
chromatin domains and nucleosome array folding regulated? 3) How is gene expression regulated
post-transcriptionally at a global scale? We will use the combination of genomics, molecular genetics,
EM, modeling and biochemistry to identify novel mechanisms by which highly conserved chromatin
regulators function to massively reprogram chromatin in a genome-wide scale. In the long run, these
studies will allow us to compare and integrate the principles of chromatin regulation throughout the
mitotic cell-cycle and quiescence, such that we can obtain the full picture of chromatin regulation.

## Key facts

- **NIH application ID:** 10645489
- **Project number:** 6R35GM139429-03
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** TOSHIO TSUKIYAMA
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $740,592
- **Award type:** 6
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645489

## Citation

> US National Institutes of Health, RePORTER application 10645489, Molecular mechanisms and functions of global chromatin control (6R35GM139429-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10645489. Licensed CC0.

---

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