# Dynamic DNA Modifications in Brain and Diseases

> **NIH NIH R35** · EMORY UNIVERSITY · 2021 · $853,907

## Abstract

Epigenetics is broadly defined as the heritable changes in gene expression and function that do
not alter DNA sequence. As an intermediate regulatory paradigm between DNA sequences and
gene expression, epigenetic mechanisms can exert substantial influence on brain development
on a scale that we are only beginning to appreciate. Furthermore increasing evidence indicates
that multiple neurodevelopmental, neurodegenerative, and psychiatric disorders are caused, at
least in part, by aberrant epigenetic modifications. Cytosine methylation serves as a critical
epigenetic mark by modifying DNA-protein interactions that influence transcriptional states and
cellular identity. 5-methylcytosine (5mC) has generally been viewed as a stable covalent
modification to DNA; however, the fact that 5-mC can be enzymatically modified to 5-
hydroxymethylcytosine (5hmC) by Tet family proteins through Fe(II) α-KG-dependent
hydroxylation gives a new perspective on the previously observed plasticity in 5mC-dependent
regulatory processes. Epigenetic plasticity in DNA methylation-related regulatory processes
influences activity-dependent gene regulation and learning and memory in the central nervous
system (CNS). Hydroxylation of 5mC to 5hmC presents a particularly intriguing epigenetic
regulatory paradigm in the mammalian brain, where its dynamic regulation is critical. Emerging
evidence also suggests potential epigenetic roles for a novel DNA adenosine modification, N6-
methyladenine (N6mA). Thus the discovery of both 5hmC/5fC/5caC and N6mA in mammalian
genome significantly increases the DNA epigenetic complexity and intriguingly all these
modifications are enriched in brain. The proposed works here will integrate various disciplines
(genetics/genomics, bioinformatics, biochemistry, and cell biology) to understand the crosstalk
among the dynamic DNA modifications during neurodevelopment and aging, and their roles in
the pathogenesis of neurological disorders.

## Key facts

- **NIH application ID:** 10221067
- **Project number:** 5R35NS111602-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** PENG JIN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $853,907
- **Award type:** 5
- **Project period:** 2019-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221067

## Citation

> US National Institutes of Health, RePORTER application 10221067, Dynamic DNA Modifications in Brain and Diseases (5R35NS111602-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221067. Licensed CC0.

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