# Epigenomic modulation of psychostimulant-inducible Fosb in the nucleus accumbens

> **NIH NIH F32** · DUKE UNIVERSITY · 2020 · $43,601

## Abstract

Project Summary/Abstract
Stimulus-inducible gene transcription ties changes in neuronal activity to the adaptations of neuronal and
synaptic function that underlie long-lasting, environmentally-induced changes in circuit dynamics. Epigenomic
modifications of chromatin, including histone acetylation, are proposed to regulate this process by tuning the
likelihood or magnitude of gene transcription. In the Nucleus Accumbens (NAc), the psychostimulant-inducible
gene Fosb is critical for generating the long-term cellular plasticity underlying addictive-like behavior, and
histones at its promoter are acetylated in response to psychostimulant exposure. It remains unknown,
however, whether the regulation of histone acetylation is causative for psychostimulant-induced changes in
FosB expression and the development of addictive-like behaviors. This proposal will utilize a novel strain of
CRISPR/dCas9 transgenic mice to directly alter the chromatin landscape at the Fosb promoter through
delivery of the acetyltransferase enzymatic core domain of p300 (dCas9-p300core), which increases acetylation
in the targeted region. Our previous data show that editing histone acetylation leaves the temporal stimulus-
dependent expression of inducible genes intact, while augmenting or depressing the amplitude of induced
gene expression. Thus, we can use this epigenome editing method to assess the specific functions of stimulus
regulation of Fosb in vivo. Aim 1 will utilize in vivo drug exposure paradigms known to produce heightened
Fosb expression in specific cell populations of the Nucleus Accumbens to test the hypothesis that delivery of
p300 to the Fosb promoter enhances Fosb expression preferentially in the activated cell ensemble. Aim 2 will
test how acetylation at the Fosb promoter affects sensitivity to the locomotor and rewarding properties of
psychostimulants. Taken together, these data will develop a novel experimental approach that can be used to
assess the mechanisms by which epigenetic regulation of psychostimulant-inducible genes modulates the
development of addictive-like behaviors.

## Key facts

- **NIH application ID:** 10068126
- **Project number:** 1F32DA052184-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Katherine Rose Tonn Eisinger
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,601
- **Award type:** 1
- **Project period:** 2020-07-01 → 2021-02-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068126

## Citation

> US National Institutes of Health, RePORTER application 10068126, Epigenomic modulation of psychostimulant-inducible Fosb in the nucleus accumbens (1F32DA052184-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10068126. Licensed CC0.

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