# Histone H2A.X signaling and chromatin remodeling in late erythropoiesis

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2022 · $302,060

## Abstract

Erythropoiesis is a process of enormous magnitude, with the average adult producing approximately 2.5 million
red blood cells each second. To maintain this impressive output, terminal erythroid maturation is coupled with
rapid proliferation. In the span of 3-4 cell divisions, erythroid cells must condense their nuclei to approximately
1/10th of their original volume in anticipation of enucleation, which involves a dramatic compaction of the
erythroid genome. Disruption this process is associated with myelodysplastic syndromes (MDS) and
congenital anemias. The mechanisms involved, however, are poorly understood. Recent evidence from our
group and others has implicated the variant histone H2A.X as an important component in normal erythroid
maturation. Phosphorylation of this histone at S139 (γ-H2A.X) is an early feature of DNA repair pathways and
contributes to the stability of broadly-distributed “foci” of DNA repair factors. Notably, we observe a burst of γ-
H2A.X foci at a specific stage of erythroid maturation, concomitant with a significant increase in proliferation
and replication rate, and with the final stages of nuclear condensation. Based on this and other observations,
we hypothesize that histone H2A.X phosphorylation signals directly to downstream pathways that accomplish
chromatin remodeling (through histone exchange) and compaction (through the induction of an apoptotic-
related pathway). These studies will provide mechanistic insight into the still-opaque processes involved in
terminal erythroid maturation, enhance our understanding of epigenetic gene regulation and chromatin
compaction, and illuminate the basis for defects in erythropoiesis that can cause anemia.

## Key facts

- **NIH application ID:** 10432108
- **Project number:** 5R01HL158848-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** MICHAEL D BULGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $302,060
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432108

## Citation

> US National Institutes of Health, RePORTER application 10432108, Histone H2A.X signaling and chromatin remodeling in late erythropoiesis (5R01HL158848-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10432108. Licensed CC0.

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