# Capturing the dynamic epigenome using single molecule and single cell approaches

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $82,268

## Abstract

ABSTRACT
Our bodies consist of billions of genetically identical cells that can exhibit distinct phenotypic or epigenetic
states. The covalent and reversible modification of histones enables cells to establish heritable gene
expression patterns without altering their genetic blueprint. Epigenetic mechanisms that control gene
expression are essential to maintain cellular identity and program multicellular differentiation. Histone H3 lysine
9 methylation (H3K9me) is associated with transcription silencing and heterochromatin formation. Fission yeast
(S. pombe) has a minimalist heterochromatin architecture that is amenable to high-throughput genetics and
biochemistry. A trio of conserved proteins regulates heterochromatin, which includes, 1) an H3K9me specific
''writer,'' Clr4Suv39h that catalyzes H3K9me 2) an H3K9me specific ''reader,'' Swi6HP1 that binds to H3K9me
chromatin and silences transcription and, 3) an H3K9me specific ''eraser,'' Epe1JmjC, that opposes
heterochromatin assembly and epigenetic inheritance. Fusing Clr4 to the tetracycline-inducible TetR DNA
binding domain facilitates rapid and reversible control of heterochromatin assembly. My lab’s innovative
genetic strategy has enabled us to identify chromatin-associated factors with unique roles that are restricted to
heterochromatin maintenance. As part of the Research Supplements to Promote Diversity in Health-Related
Research program, the supplemental funding request will investigate the mechanisms that influence epigenetic
silencing downstream of H3K9 methylation establishment. Specifically, the graduate student supported by this
application will use in vitro reconstitution and single-molecule approaches to investigate the dynamic chromatin
rearrangements that lead to epigenetic silencing. The supplement award will promote the research, career and
professional training of a graduate student belonging to an NIH designated underrepresented category. The
program of research outlined in this application is well-aligned and collaboratively developed with the
candidate’s future career aspirations. Furthermore, all of the scientific goals described here are fully consistent
with the proposed research directions of the parent award.

## Key facts

- **NIH application ID:** 10402130
- **Project number:** 3R35GM137832-02S2
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kaushik Ragunathan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $82,268
- **Award type:** 3
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402130

## Citation

> US National Institutes of Health, RePORTER application 10402130, Capturing the dynamic epigenome using single molecule and single cell approaches (3R35GM137832-02S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10402130. Licensed CC0.

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