# Investigating chromatin mechanisms using viral systems

> **NIH NIH R35** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2022 · $31,925

## Abstract

PROJECT SUMMARY
All eukaryotic genomes are compacted in a fundamental assembly called chromatin, the aberrant regulation of
which is a hallmark of many diseases and cancers. Technologies to study chromatin have advanced significantly
in recent years, allowing us to progress from linear sequencing to 3D chromosome conformation studies.
However, it is becoming increasingly clear that chromatin states are dynamic and respond to perturbations. Thus
a barrier remains to understanding the biological functions of chromatin in a dynamic system, and not merely at
the baseline state. Viruses have evolved to take over the cell to produce viral progeny, necessarily hijacking
cellular chromatin for viral benefit, thereby providing an ideal dynamic system in which to interrogate chromatin
state changes. Moreover, the study of virus-host interactions has been doubly beneficial by leading to advances
in virus biology and to discoveries of some of the most important areas of molecular biology, from splicing to
p53. Due to the advances in sequencing technology, we are now ideally positioned to take the next step to
understanding chromatin in the context of biological changes. In this proposal, we aim to merge cutting-edge
chromatin technology with virus infection to reveal fundamental chromatin functions. We use two
different nuclear replicating viruses, adenovirus and herpesvirus, as the test cases for virus infection to pinpoint
chromatin vulnerabilities exploited by multiple pathogens. We have identified a viral packaging protein from
adenovirus, protein VII, that causes global chromatin reorganization and we will systematically dissect the
mechanisms by which this reorganization occurs. Our preliminary results suggest that protein VII, together with
cellular binding partners, may replace linker histones thus revealing a previously unknown vulnerability of
chromatin. We have also uncovered that herpes simplex virus incorporates the histone variant macroH2A1 on
its genome during infection. MacroH2A1 has been described as a marker of both silencing and an activating
chromatin, therefore, we will use this scenario to untangle the long-standing enigma of macroH2A1 function.
Completion of the proposed studies will generate new chromatin targets and facilitate development of innovative
therapies for cancer, inflammation, and viral diseases.

## Key facts

- **NIH application ID:** 10481687
- **Project number:** 3R35GM133441-03S2
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Daphne Christina Avgousti
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,925
- **Award type:** 3
- **Project period:** 2019-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10481687

## Citation

> US National Institutes of Health, RePORTER application 10481687, Investigating chromatin mechanisms using viral systems (3R35GM133441-03S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10481687. Licensed CC0.

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