# Investigating the epigenetic mechanisms surrounding neuronal stem cell differentiation

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2020 · $45,520

## Abstract

Project Summary/Abstract
Chromatin, formed from highly regulated interactions of DNA with the histone proteins
(H2A, H2B, H3 and H4), helps eukaryotes regulate genome integrity, transcriptional, and
epigenetic pathways. Histone proteins can be post-translationally modified (PTM) at
select residues, which include lysine methylation and acetylation. These histone
PTMs recruit protein complexes that further modulate the activity of the nearby
chromatin environment (Jenuwein and Allis et. al., 2001). However, the mechanistic
details of how histone PTMs modify enzymatic activities on chromatin remain poorly
understood. Previously, our lab discovered a novel histone PTM on histone
H3, H3K23me3, which protects highly repetitive regions of the genome during meiosis
in T. thermophila and C. elegans (Papazyan et. al., 2014). Recently we showed that a
lysine demethylase, KDM4B, selectively associates with H3K23me3 in differentiating
mammalian sperm and that the H3K23me3-KDM4B interaction leads to demethylation of
H3K36me3, in vitro (Su et. al., 2016). A combination of published work (Fujiwara et. al.,
2016) and unpublished data from our lab show that both H3K23me3 and KDM4B are also
highly enriched in newly differentiated mammalian neurons in brain tissue and in cultured
neurons. Interestingly, this published work also found that mutations in the KDM4 family
are associated with neurodevelopmental diseases, but other sites of histone
demethylation, by KDM4B, are not known. Based on our previous findings, I hypothesize
that the H3K23me3-KDM4B interaction protects chromatin of differentiating neurons
against DNA damage during differentiation. This project aims to unravel the molecular
mechanisms surrounding the chromatin dynamics of differentiating mammalian neurons.
My overall goal of this proposal is to better understand the roles of H3K23me3 and
KDM4B during neuronal differentiation.

## Key facts

- **NIH application ID:** 9968290
- **Project number:** 5F31GM130114-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** David Alexander Vinson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-07-15 → 2022-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968290

## Citation

> US National Institutes of Health, RePORTER application 9968290, Investigating the epigenetic mechanisms surrounding neuronal stem cell differentiation (5F31GM130114-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968290. Licensed CC0.

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