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

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $50,490

## Abstract

Abstract
Our bodies consist of billions of genetically identical cells with the capacity to exhibit
distinct phenotypic or epigenetic states. The establishment of epigenetic states, in part,
depends on the covalent and reversible modification of DNA packaging proteins called
histones. Histone H3 lysine 9 methylation (H3K9me) is associated with transcriptional
gene silencing and heterochromatin formation. This process underpins normal centromere
and telomere function, transposon silencing and the inactivation of repetitive DNA
elements. The loss of heterochromatin in cells is associated with chromosome segregation
defects, and genome instability. Our long term goal is to identify and reconstitute
heterochromatin dependent protein interactions and capture how these dynamic
processes alter heritable gene expression states in single cells and individual lineages.
Although histones are partitioned between daughter strands during DNA replication, it
remains unclear as to whether the modifications themselves are sufficient to act as carriers
of epigenetic memory. The prevailing notion is that a balance of enzymatic activities
between proteins that can read, write and erase histone modifications alters the stability
and heritability of epigenetic states. Our recent studies have revealed that proteins
previously thought to act as histone modifying enzymes proteins play structural or non-
enzymatic roles that profoundly impact heterochromatin stability. Using fission yeast,
Schizosaccharomyces pombe, as a model system, the major goals of this proposal are 1)
to biochemically define and reconstitute heterochromatin dependent protein interactions
that are implicated in epigenetic inheritance 2) identify factors that coordinate parental
histone transfer with DNA replication to ensure that epigenetic memory is passed on from
parental cells to daughter cells following cell division 3) capture the cellular trajectory
leading to the establishment of ad hoc or adaptive epigenetic states in response to acute
genomic stress. We expect that our studies will identify new regulatory mechanisms that
impact heterochromatin assembly and inheritance in addition to discovering how cells
leverage these pathways to respond to acute changes in genomic homeostasis.
.

## Key facts

- **NIH application ID:** 10386079
- **Project number:** 3R35GM137832-02S1
- **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:** $50,490
- **Award type:** 3
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386079

## Citation

> US National Institutes of Health, RePORTER application 10386079, Capturing the dynamic epigenome using single molecule and single cell approaches (3R35GM137832-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10386079. Licensed CC0.

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