# ROLE OF EZH2 MEDIATED EPIGENETIC CHANGES AND INCREASED DRINKING IN ADULTHOOD BY ADOLESCENT ALCOHOL EXPOSURE

> **NIH NIH F32** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $8,843

## Abstract

Project Summary/Abstract
Adolescent alcohol use is significant risk factor for the development of alcohol use disorders or other
psychiatric disorders later in life, however the molecular changes that mediate this are largely unknown.
Previous studies suggest that epigenetic reprogramming in the adult amygdala due to adolescent alcohol
exposure may be responsible for adult psychopathology. It has been shown that enhancer of zeste homolog 2
(EZH2), which is a major component of the polycomb repressive complex 2, is important in brain maturation.
Additionally, preliminary data from both rodent models of adolescent alcohol exposure and human postmortem
amygdala, suggest that EZH2 may be an important regulator of epigenetic changes that occur after adolescent
alcohol exposure. However, its role in epigenetic reprogramming at a candidate gene or whole genome level or
its role in regulating anxiety and increased drinking in adulthood after adolescent alcohol exposure is unknown.
This proposal will evaluate the role of EZH2 through a number of different approaches including brain region-
specific pharmacological and genetic intervention, and whole-genome sequencing approaches to determine
the role of EZH2 in mediating molecular, epigenetic, synaptic, and behavioral changes that occur after
adolescent alcohol exposure. EZH2 will be characterized in different subregions of the amygdala using
immunohistochemical and fluorescent in situ hybridization after adolescent alcohol exposure. Pharmacological
and genetic inhibition will be used to determine if inhibition of EZH2 in the central nucleus of amygdala (CeA)
attenuates anxiety-like behavior and higher alcohol consumption caused by adolescent alcohol exposure, and
subsequent molecular and anatomical (spine density) outputs in adulthood. Chromatin immunoprecipitation
sequencing will be used to analyze changes in EZH2 occupancy throughout the whole genome and identify
novel gene hubs and gene network pathways that are disrupted by EZH2 after adolescent alcohol exposure.
These results will determine the tractability of EZH2 as a novel therapeutic intervention for the use in alcohol
use disorders in individuals who began drinking during adolescence.

## Key facts

- **NIH application ID:** 9999382
- **Project number:** 5F32AA027410-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** JOHN P BOHNSACK
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $8,843
- **Award type:** 5
- **Project period:** 2018-09-27 → 2020-10-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999382

## Citation

> US National Institutes of Health, RePORTER application 9999382, ROLE OF EZH2 MEDIATED EPIGENETIC CHANGES AND INCREASED DRINKING IN ADULTHOOD BY ADOLESCENT ALCOHOL EXPOSURE (5F32AA027410-03). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9999382. Licensed CC0.

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