# Molecular Mechanisms of Chromatin Recognition

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $382,895

## Abstract

ABSTRACT
By displaying combinatorial patterns of chemical modifications, the nucleosome serves as a signaling
hub in chromatin-templated processes, including gene expression, replication, and DNA damage repair.
These processes are critical to the maintenance of cellular identity and genomic integrity and their
misregulation is a hallmark of cancer and many developmental diseases. Despite this clear connection
to human health, our understanding of nucleosome recognition by chromatin modifying enzymes and
effectors of chromatin-templated processes is incomplete. Moreover, we lack fundamental molecular
insights into how combinatorial chromatin modification signatures function and the interplay between
chromatin modifications. These knowledge deficits are limiting in the development of therapeutics
targeting chromatin processes. To address this unmet need, we are exploring mechanisms of
nucleosome recognition and signaling on multiple scales. We have used proteomics to define the
nucleosome interactome and identify two key regions on the nucleosome surface that dominant
nucleosome binding. We are now exploring these regions at higher resolution and interrogating the role
of chromatin modifications in tuning nucleosome interactions. Meanwhile, we are exploring
mechanisms governing the interplay between histone modifications at near atomic resolution. By
pairing semisynthetic designer nucleosomes with cryo-electron microscopy and X-ray crystallography,
we propose to visualize chromatin enzymes in action on modified nucleosome substrates. Through
these studies, we expect to define universal patterns of chromatin recognition and elucidate molecular
mechanisms through which chromatin proteins function. Our research will enable hypothesis-driven
functional studies in disease model systems and uncover new avenues for drug discovery.

## Key facts

- **NIH application ID:** 10225568
- **Project number:** 5R35GM133498-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Robert McGinty
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,895
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225568

## Citation

> US National Institutes of Health, RePORTER application 10225568, Molecular Mechanisms of Chromatin Recognition (5R35GM133498-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225568. Licensed CC0.

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