# Molecular Mechanisms Underlying the Regulation of Local Chromatin Structure

> **NIH NIH R35** · UNIVERSITY OF TEXAS DALLAS · 2021 · $382,500

## Abstract

PROPOSAL SUMMARY
 The packaging of genomic DNA into repeating nucleosome units plays a pivotal role in the regulation of
essential biological process including DNA transcription, DNA replication, and DNA repair. Cells must assemble
and disassemble nucleosomes to read the information stored in the DNA sequence in a temporally and spatially
regulated way. As such, cells have evolved several mechanisms that precisely regulate nucleosome dynamics
and influence the local structure of chromatin. These mechanisms include: (1) the incorporation of histone
variants into the nucleosome, (2) post-translational modification of histones, (3) histone chaperone activity, (4)
ATP-dependent nucleosome remodeling, and (5) nucleosome-binding proteins. We currently do not know how
these mechanisms act synergistically, nor how they influence intrinsic nucleosome dynamics.
 The research proposed in this MIRA application will focus on the quantification of nucleosome dynamics
and the molecular basis of its regulation. We will develop a high-throughput assay for the quantification of
nucleosome dynamics that will be applied to nucleosome assembly intermediates, mono-nucleosomes and multi-
nucleosome arrays. This assay revolves around hydrogen-deuterium exchange analysis chromatin substrates
in varied biologically-relevant states. We will also characterize the molecular mechanisms underpinning
concerted activity of histone chaperones and histone acetyltransferases. Systems of interest at Rtt109, Vps75
and Asf1; as well as Nap1, CBP/p300 and linker histone H1. Varied approaches will be employed including
biochemistry, high-resolution structural characterization, and in vivo complex analysis. The proposed work will
impact translational studies motivated to develop anti-fungal therapeutics and identify new avenues for targeting
of anti-cancer treatments.

## Key facts

- **NIH application ID:** 10201668
- **Project number:** 5R35GM133751-03
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Sheena D'Arcy
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201668

## Citation

> US National Institutes of Health, RePORTER application 10201668, Molecular Mechanisms Underlying the Regulation of Local Chromatin Structure (5R35GM133751-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201668. Licensed CC0.

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