# Mechanism of PRC2-mediated Gene Silencing during Cardiomyocyte Differentiation

> **NIH NIH F30** · UNIVERSITY OF COLORADO · 2021 · $51,036

## Abstract

Project Summary 
Cardiomyocytes require precise gene regulation programs to prevent pathophysiology. Upregulation of cardiac 
remodeling genes results in cardiomyocyte hypertrophy and decreased heart function. While much is known 
about the transcription factors that drive cardiomyocyte specific gene expression, we have a limited 
understanding of how histone posttranslational modifications regulate cardiomyocyte development and 
maintenance. Polycomb Repressive Complex 2 (PRC2) is a histone modifying complex that silences gene 
expression by tri-­methylating lysine 27 on histone H3. Conditional knockout studies show the absence of 
PRC2, during mouse heart development, results in upregulation of cardiomyocyte specific transcription factors 
and cardiac hypertrophy. However, there is a lack of mechanistic understanding regarding how PRC2 
regulates cardiomyocyte specific genes. Emerging evidence demonstrates that human PRC2 is recruited to 
chromatin through an interaction with a set of accessory proteins known as AEBP2 and PCL proteins. This 
proposal will utilize PRC2 separation-­of-­function mutations to test the hypothesis that the interaction between 
PRC2 and these accessory proteins is necessary for regulating cardiomyocyte specific genes and for 
preventing cardiomyocyte hypertrophy. High-­throughput sequencing and immunocytochemistry approaches 
will be used to determine whether AEBP2 or PCL proteins is/are responsible for maintaining the transcriptional 
profile and phenotype of cardiomyocytes in a PRC2 dependent manner. Furthermore, live-­cell single-­molecule 
imaging will be used to define how AEBP2 and PCL proteins affect the chromatin-­binding dynamics of PRC2 
throughout cardiomyocyte differentiation. The experiments in this proposal represent a critical step toward 
uncovering the mechanism of PRC2 mediated gene-­silencing in cardiomyocytes, a mechanism that is central 
to normal heart development and function.  
Training Plan Summary: The proposed research will be completed in the University of Colorado Boulder 
Biochemistry Department, located in the multidisciplinary BioFrontiers Biotechnology building. The applicant 
will draw from local expertise in the fields of cardiomyocyte biology, computational biology, chromatin biology, 
and transcriptional regulation to develop into an independent physician-­scientist that is well versed in 
mechanisms of gene regulation. The applicant’s training plan includes taking coursework, receiving individual 
mentorship, attending conferences, giving oral presentations, and preparing/submitting manuscripts.

## Key facts

- **NIH application ID:** 10166911
- **Project number:** 5F30HL147499-03
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Daniel Thomas Youmans
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-05-15 → 2023-05-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166911

## Citation

> US National Institutes of Health, RePORTER application 10166911, Mechanism of PRC2-mediated Gene Silencing during Cardiomyocyte Differentiation (5F30HL147499-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10166911. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*