# Elucidation of the PRC2 interactome in early human neural development

> **NIH NIH F32** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $65,606

## Abstract

Project Summary
My research investigates the mechanisms by which epigenetic modifiers regulate the developing
mammalian brain. The mammalian brain contains well over 1010 neurons, which synapse together to
perform multiple functions including but not limited to sensation, cognition, and conscious thought. These
vast numbers of cells all originate from a relatively small pool of neural progenitors, which divide and
differentiate in response to spatiotemporal clues during embryonic development. The correct development
and function of these cells requires exquisitely accurate gene expression control that is mediated by both
transcription factors and epigenetic modifiers. While mutations in transcription factors are well
characterized for causing neurodevelopmental defects, little is known about the mechanisms by which
epigenetic modifier mutations cause neurodevelopmental defects. This project will begin filling this gap by
analyzing the Polycomb Repressive Complex 2 (PRC2) complex, an epigenetic modifier that methylates
lysine 27 of histone H3 (H3K27me3), regulates RNA polymerase II transcription, and is necessary for
neural progenitor formation and function. Specifically, my project will investigate the regulation of PRC2
function and gene targeting within neural progenitor cells as they proliferate and differentiate to neuronal
fates. Using immunoprecipitation-mass spectrometry, we recently identified a novel interaction between a
PRC2 component and a key neurogenesis determinant, which likely has a never-discovered function in
gene regulation. We will use multidisciplinary approaches to establish the mechanistic details of this
interaction and to elucidate how these interactions affect PRC2 function. To achieve this goal, we will first
biochemically identify the protein domains or amino acids required for this molecular interaction. Next, we
will determine how this neurogenesis determinant affects PRC2 binding to gene targets and influences
transcription activities. Finally, we will delineate the effect of this interaction on the self-renewal and
differentiation capacity of neural progenitors. Our findings will reveal the molecular mechanism by which a
crucial neurogenesis determinant interacts with PRC2 to program gene expression required for early
neurogenesis. My research uses multiple tools to elucidate mechanisms by which epigenetic modifiers
regulate early neural development. The long-term goal of my studies is to define the cross-talk between
chromatin modifiers and transcriptional circuitry in regulating gene expression in developmental contexts
and to determine how dysfunction in this cross-talk contributes to human birth defects and diseases.

## Key facts

- **NIH application ID:** 9856467
- **Project number:** 5F32HD093276-03
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Myron K Evans
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,606
- **Award type:** 5
- **Project period:** 2018-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856467

## Citation

> US National Institutes of Health, RePORTER application 9856467, Elucidation of the PRC2 interactome in early human neural development (5F32HD093276-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9856467. Licensed CC0.

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