# Role of Multimerization in H3.3/H4 deposition by the HIRA complex

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $46,036

## Abstract

Project Summary
The goal of this project is to characterize, with molecular detail, the role that multimerization of the
HIRA histone chaperone complex plays in depositing histone H3.3/H4 onto DNA. In order to fit
roughly two meters worth of DNA into a ten-micron cell nucleus, histones are used as scaffolding
proteins to condense linear genetic material into the higher order structures of chromatin. Epigenetic
regulatory machinery is essential to ensure that the chromatin landscape is well maintained to allow
for certain gene expressions to be readily activated or inactivated to regulate both cell fate and cell
stability. The HIRA histone chaperone complex is responsible for delivering histone H3.3/H4 onto
nascent DNA in areas of active gene transcription and is therefore implicated in chromatin changes
during development, in maintenance of terminally differentiated cell types, and in aging. The
strategies I propose will first provide understanding of the molecular basis of the interaction between
the C-terminal trimerization domain of HIRA and CABIN1 and then will probe the relevance of these
interactions in vitro by investigating the effect that mutants have on the histone deposition process
using a nucleosome assembly assay and in cells by investigating the effect that mutants have on
complex localization and histone deposition within the crowded nuclear landscape. The proposed
study will deepen our understanding of a ubiquitous epigenetic mechanism essential for regulating
the chromatin environment of healthy human cells.

## Key facts

- **NIH application ID:** 10139844
- **Project number:** 1F31AG067692-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Mary Szurgot
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-03-03 → 2024-03-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139844

## Citation

> US National Institutes of Health, RePORTER application 10139844, Role of Multimerization in H3.3/H4 deposition by the HIRA complex (1F31AG067692-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10139844. Licensed CC0.

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