# Mechanisms of chromatin and transcriptional regulation

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $561,780

## Abstract

Histone post-translational modifications (PTMs), chromatin-remodeling enzymes, DNA
methylation, and histone chaperones play critical roles in the organization and control of
our genomes. Importantly, disruption or mutation of the proteins or enzymes responsible
for chromatin regulation underlies a number of human diseases, most notably cancer.
Our long-term goal is to elucidate the molecular underpinnings of chromatin regulation
and define how this regulation contributes to human biology and disease. Our lab has
spearheaded the pursuit of this goal, making seminal discoveries that explain how the
chromatin-modifying machinery “writes” and “reads” histone PTMs and how histone
PTMs function in transcription, DNA replication, DNA repair, and maintenance of DNA
methylation. Yet, despite considerable progress, there remain many crucial knowledge
gaps. For example, it is largely unknown the extent to which histone PTMs function in a
combinatorial manner. Similarly, we do not fully understand the biochemical basis for
recognition of histone PTMs by the many different reader domains in chromatin-
associated proteins nor do we fully understand how paired reader domains bind
nucleosomes in a multivalent manner. Finally, we do not know the functions of newly
identified histone PTMs, e.g., lysine crotonylation. With this MIRA award, our lab will
close these knowledge gaps by answering three of the foremost fundamental questions
in chromatin biology: 1) How do histone-modifying enzymes and chaperones regulate
transcription, the cell cycle, and maintain chromatin integrity? 2) How do recently
discovered histone PTMs such as crotonylation contribute to gene regulation? 3) To
what extent do histone PTMs collaborate to regulate downstream functions in
chromatin?
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## Key facts

- **NIH application ID:** 10136452
- **Project number:** 5R35GM126900-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Brian D Strahl
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $561,780
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136452

## Citation

> US National Institutes of Health, RePORTER application 10136452, Mechanisms of chromatin and transcriptional regulation (5R35GM126900-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10136452. Licensed CC0.

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