# The Role of Histone Variant H3.3 Regulation by Hira in Hematopoiesis

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2020 · $45,520

## Abstract

Abstract
Hematopoiesis must be sustained throughout life in order to maintain immune response capabilities and to
replenish blood supplies. A large proportion of adult HSCs therefore remain quiescent, rarely undergoing cell
division, until they become activated upon bodily insults, such as infection and blood loss. These quiescent
HSCs must undergo global changes in gene expression patterns in order to leave their dormant state and
differentiate. Chromatin modifiers that act independently of cell division may therefore be of particular
importance in regulating the behavior of quiescent HSC through the establishment of the chromatin landscape
differentially across the genome. One such chromatin modifier is the histone variant H3.3 chaperone Hira,
which is responsible for incorporating H3.3 independent of DNA replication at poised and transcriptionally
active promoters. Despite the fact that this histone variant only differs from the conventional H3 histones by
four or five amino acids, its gene-specific association is required for proper establishment of gene expression
and lineage specification in murine embryonic stem cells (mESC), post-mitotic neurons, and oocytes. Since
Hira deposits H3.3 independently of S phase, we are testing the hypothesis that Hira plays a critical role in the
maintenance of quiescent HSCs, since quiescent HSCs will need cell division-independent mechanisms to
regulate H3.3. The early results from this study demonstrate a requirement for the histone chaperone Hira in
HSC quiescence and self-renewal behaviors. We will next assess the ability of Hira-mediated H3.3
incorporation to maintain normal HSC activity and gene expression patterns. Knowledge gained from this study
regarding in vivo HSC epigenetic state regulation may inform future research for clinical applications, such as
for improved methods of in vitro HSC expansion. Characterizing the importance of H3.3 incorporation and
turnover by Hira in normal HSC activity will therefore provide invaluable information regarding the epigenetic
regulation of hematopoietic homeostasis.
Rebecca Murdaugh will conduct the research proposed in this application over the course of 4 years. She is a
graduate student in the second year of her PhD with undergraduate training in biochemistry and cell and
molecular biology.

## Key facts

- **NIH application ID:** 9957054
- **Project number:** 5F31DK112542-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Rebecca Lauren Murdaugh
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2017-06-20 → 2021-06-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957054

## Citation

> US National Institutes of Health, RePORTER application 9957054, The Role of Histone Variant H3.3 Regulation by Hira in Hematopoiesis (5F31DK112542-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9957054. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*