# Molecular mechanisms of chromatin and epigenetic regulation

> **NIH NIH R35** · VAN ANDEL RESEARCH INSTITUTE · 2021 · $475,000

## Abstract

PROJECT SUMMARY
The long-term goal of our research program is to define molecular mechanisms regulating chromatin
modification signaling. We are particularly interested in understanding the complex relationship between DNA
methylation and histone posttranslational modifications; two key epigenetic regulators of genome accessibility
and function. Within this broad framework, we question 1) how are the writers and erasers of chromatin
modifications regulated, 2) how do nuclear proteins and their complexes interface with (i.e., read) epigenetic
marks to perform their chromatin regulatory functions, and 3) how does deregulation of chromatin signaling
contribute to human disease? Our current studies are focused on UHRF1, an E3 ubiquitin ligase that is the
cornerstone of a pathway responsible for maintaining a major portion of the DNA methylation found in
mammalian cells. We recently showed that UHRF1 functions as a key regulator of DNA methylation
inheritance through its interconnected reader and writer activities toward histone H3. While details of how
UHRF1 performs its regulatory function are beginning to be uncovered, major gaps in knowledge exist in our
basic molecular understanding of DNA methylation regulation and the role of UHRF1 in this process. Projects
in the lab under this framework will question 1) how does UHRF1 interact with and modify chromatin, 2) what is
the relationship between UHRF1, DNA methylation, and genome accessibility, 3) what is the role of histone
ubiquitination in DNA methylation regulation, and 4) how does the structurally related protein UHRF2 regulate
DNA methylation? Through a multidisciplinary and collaborative research program that leverages strengths in
biochemical, biophysical, structural, genomic, proteomic, and cell-based studies of chromatin and epigenetic
regulation, we hope to translate basic knowledge of epigenetic mechanism into therapeutic benefit.

## Key facts

- **NIH application ID:** 10229452
- **Project number:** 5R35GM124736-05
- **Recipient organization:** VAN ANDEL RESEARCH INSTITUTE
- **Principal Investigator:** Scott Rothbart
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $475,000
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229452

## Citation

> US National Institutes of Health, RePORTER application 10229452, Molecular mechanisms of chromatin and epigenetic regulation (5R35GM124736-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10229452. Licensed CC0.

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