# ILLUMINATION OF CHROMATIN REGULATION VIA CHEMICAL CONTROLLED PROXIMITY

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $440,289

## Abstract

Project Summary
The overarching goal of this project is to understand at a mechanistic level the chromatin
regulatory pathways governing gene expression. To achieve this objective, we use
chemically controlled proximity to allow for temporal and special control over specific
chromatin regulatory enzymes. Our research group has made contributions to
understanding the interplay between the heterochromatin protein 1 gene repression
pathway and other chromatin regulators. In addition, we have a drug discovery program
that has identified inhibitors of heterochromatin gene repression. We also have developed
bifunctional molecules that work with catalytically inactive dCas9 to recruit endogenous
chromatin regulatory enzymes to any site across the mammalian genome. Three main
goals of this research program are: 1. Explore how heterochromatin gene repression is
governed by two distinct H3K9 methylation binding proteins, 2. Develop approaches to
visualize dynamic heterochromatin gene repression in real time at the single cell level 3.
Study chromatin dynamics in real time with bifunctional compounds to recruit endogenous
enzymes to specific loci. Over the course of this grant our research group will continue to
advance our understanding of the mechanisms of heterochromatin gene repression using
unique chemically based technologies. We also will further advance areas we have
pioneered developing bifunctional small molecules to explore the capture and retargeting
of endogenous chromatin regulators as an approach to understanding mammalian
genome regulation.

## Key facts

- **NIH application ID:** 10842222
- **Project number:** 5R35GM148365-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nathaniel A. Hathaway
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $440,289
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842222

## Citation

> US National Institutes of Health, RePORTER application 10842222, ILLUMINATION OF CHROMATIN REGULATION VIA CHEMICAL CONTROLLED PROXIMITY (5R35GM148365-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842222. Licensed CC0.

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