# MECHANISM OF HP1-MEDIATED HETEROCHROMATIN ASSEMBLY AND DURABILITY IN LIVE CELLS

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $43,167

## Abstract

Project Summary/Abstract
My laboratory studies gene regulation dynamics in mouse embryonic stem cells and fibroblast tissues. We use
these model systems to investigate the mechanics of chromatin regulatory pathways that provide stability to
gene expression profiles through cell division allowing for mammalian tissue identity. Preservation of
heterochromatin-mediated gene repression is critical for development and it is dysregulated in a number of
human diseases. Yet, the molecular mechanics of formation and memory of heterochromatin repression
domains are poorly understood. To understand how these regulatory processes function in vivo, we developed
a novel platform that allows individual chromatin modifying activities such as Heterochromatin Protein-1 (HP1)
to be recruited with high temporal control to native chromatin substrates. We have recently improved this
system to allow us to rapidly change the structure of the endogenous chromatin substrate in order to explore
the regulation of a diverse range of promoter and gene structures. The long-term goal of this project is to
understand the mechanism of HP1-mediated gene repression and to determine the key features that provide
heterochromatin stability through successive cell generations. Specifically, in this work we examine: (1) the
influence on heterochromatin assembly of chromatin structural features such as: promoter transcriptional
activity, DNA methylation, and histone posttranslational modifications, (2) the influence of these same
chromatin features on the durability of heterochromatin gene repression. Additionally, using high throughput
screening we have discovered novel inhibitors that disrupt HP1 mediated gene repression. We will develop
these small molecule probes and use these compounds to define the role of individual enzymatic activities in
heterochromatin assembly and durable gene repression. At the conclusion of these studies, using a
combination of chemical approaches and novel in vivo tools, we will provide a new generalizable model for
how HP1-mediated heterochromatin is assembled and maintained in living cells.

## Key facts

- **NIH application ID:** 9935488
- **Project number:** 3R01GM118653-03S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nathaniel A. Hathaway
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,167
- **Award type:** 3
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935488

## Citation

> US National Institutes of Health, RePORTER application 9935488, MECHANISM OF HP1-MEDIATED HETEROCHROMATIN ASSEMBLY AND DURABILITY IN LIVE CELLS (3R01GM118653-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935488. Licensed CC0.

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