# Uncovering the function of histone variant H2BE in neurons

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2022 · $46,752

## Abstract

Project Summary
The goal of this proposal is to elucidate the molecular and behavioral function of histone variant H2BE in neurons.
Histone variants, which are encoded by separate genes, can substitute for the canonical histone proteins (H2A,
H2B, H3, and H4) and are involved in regulation of many cellular processes and gene expression. The histone
variant H2BE was discovered in the mouse main olfactory epithelium, where it affects olfactory neuron function
and longevity. While H2BE was previously thought to be exclusively expressed in the olfactory system, our lab
developed a highly specific antibody against H2BE and demonstrated that H2BE is present throughout the brain.
However, despite the importance of histone variants in controlling neuronal function, to date, H2BE remains
unstudied outside of the olfactory system. Here, I propose to determine how H2BE alters chromatin structure,
neuronal gene expression, and animal behavior. I hypothesize that H2BE decreases binding of linker histone
H1, controls expression of activity-dependent genes, and is necessary for cognitive flexibility, spatial learning,
and fear memory. To test my hypothesis, I will combine genome-wide sequencing, mouse models, and animal
behavior with molecular and biochemical techniques from the chromatin biology field. In Aim 1, I will determine
how H2BE expression alters chromatin structure. I will use ChIP-sequencing to define the genomic localization
of H2BE at baseline and in response to external signals. My preliminary data demonstrates that H2BE promotes
an open chromatin configuration and decreases binding of heterochromatin-associated proteins. Therefore, I will
examine how H2BE affects the composition of the chromatin fiber. Specifically, I will use ChIP-seq to determine
how H2BE incorporation affects localization of linker histone H1. Aim 2 addresses the role of H2BE in neuronal
gene expression and mouse behavior. First, I will test the effects of H2BE knockout on RNA-sequencing of
neurons with and without external stimulation. Second, I will perform a battery of behavioral tests using H2BE
WT and KO mice designed to determine the specific brain regions most affected by H2BE loss and to fully
characterize the role of H2BE in cognition. The work proposed here will reveal how histone variant H2BE
contributes to the complex chromatin environment in the brain. This discovery is critical to understanding how
neurons use environmental signals to control transcription and ultimately govern behavior. In developing a more
complete understanding of the chromatin landscape in neurons, we will also gain insight into potential
therapeutics for the treatment of the many neurological disorders that are linked to disruption of epigenetic
regulation in the brain.

## Key facts

- **NIH application ID:** 10462825
- **Project number:** 1F31MH126576-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Emily Ruth Feierman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462825

## Citation

> US National Institutes of Health, RePORTER application 10462825, Uncovering the function of histone variant H2BE in neurons (1F31MH126576-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462825. Licensed CC0.

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