# Investigating chromatin mechanisms using viral systems

> **NIH NIH R35** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $439,998

## 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:** 10001588
- **Project number:** 5R35GM133441-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Daphne Christina Avgousti
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $439,998
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001588

## Citation

> US National Institutes of Health, RePORTER application 10001588, Investigating chromatin mechanisms using viral systems (5R35GM133441-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001588. Licensed CC0.

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