# Investigating chromatin mechanisms using viral systems

> **NIH NIH R35** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $124,965

## Abstract

PROJECT SUMMARY
(as stated in parent grant)
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:** 10386678
- **Project number:** 3R35GM133441-03S1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Daphne Christina Avgousti
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $124,965
- **Award type:** 3
- **Project period:** 2019-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386678

## Citation

> US National Institutes of Health, RePORTER application 10386678, Investigating chromatin mechanisms using viral systems (3R35GM133441-03S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10386678. Licensed CC0.

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