# The epigenetic role of EGR1 during postnatal brain development and in neuronal activity

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2020 · $337,574

## Abstract

TITLE: The epigenetic role of EGR1 during postnatal brain development and in neuronal activity
Project Summary/Abstract
 Early growth response gene-1 (Egr1) is a critical transcription factor involved in many important biological
processes, including neuronal plasticity and memory formation. With a rapid increase in expression during the
first few weeks after birth, Egr1 controls the selection, maturation and functional integration of newborn
neurons. The regulation of Egr1-mediated gene expression has been shown to be under methylation control.
However, Egr1 target sites and their epigenetic regulation in the nervous system remains largely unknown. The
investigators have recently identified a large number of genomic loci with their cell-type specific methylation
patterns established during postnatal frontal cortex development. For both human and mouse, these loci
enrich for transcription factor binding motifs, in particular for Egr1. The CpG dinucleotides within these
predicted EGR1 binding sites become hypo-methylated in mature neurons but remain heavily methylated in
glia. In this study, the investigators propose to systematically investigate Egr1-mediated epigenetic regulatory
networks underlying the postnatal brain development. The central hypothesis is that, Egr1 is a key mediator for
gene-environment interactions shaping brain methylome during early postnatal development, and plays an
essential role in the establishment of cell-type specific DNA methylation patterns and in the epigenetic control
of activity-induced methylation changes. In Aim 1, the investigators will determine the methylation profiles of
EGR1 binding sites during postnatal brain development. In Aim 2, the investigators will determine DNA
demethylation mechanism underlying the postnatal brain development. Gain- or loss-of-function methods will
be used to manipulate Egr1 and Tet enzymes expression to test the hypothesis that increased Egr1 and Tet
enzymes expression is prerequisites for the establishment of the cell-type specifically methylation patterns on
its target sites during development. In addition, the investigators will examine whether high basal Egr1
expression is required to maintain the hypo-methylation states of its binding sites. Given the critical role of Egr1
in brain development and function, the investigators anticipate that these studies will provide important new
insights into the key epigenetic mechanisms that underlie postnatal brain development and neuronal activity.

## Key facts

- **NIH application ID:** 9948023
- **Project number:** 5R01NS094574-05
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Hehuang Xie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,574
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948023

## Citation

> US National Institutes of Health, RePORTER application 9948023, The epigenetic role of EGR1 during postnatal brain development and in neuronal activity (5R01NS094574-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948023. Licensed CC0.

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