# Mechanism and Function of Cardiac Transcriptional Repression Networks

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $536,739

## Abstract

Abstract
Congenital heart disease (CHD) remains the most common congenital malformation. Therefore,
attaining a mechanistic understanding of cardiomyocyte formation is crucial for improving
outcomes to structural heart disease. Though much emphasis in the last few years has been
placed on transcription factor networks that control cardiomyocyte differentiation, these studies
have mainly focused on transcriptional activation. However, there is growing recognition that
alterations in transcriptional repression also lead to CHDs. Transcriptional repression involves
not only cardiac transcription factors but also broadly expressed multiprotein machines that
modify and remodel chromatin. Prominent among these is the Nucleosome Remodeling and
Deacetylase (NuRD) complex. In this proposal we address the role of chromodomain helicase
DNA-binding protein 4 (CHD4), the catalytic core component of the NuRD complex. The critical
nature of CHD4 is highlighted by mutations in Chd4 being causative to CHDs. The goal of the
current application is to test the central hypothesis that CHD4 functions with the NuRD complex
to regulate cardiac chromatin architecture. This will be achieved by: 1) Determine whether CHD4
both represses and activates cardiac gene expression. 2) Delineate how CHD4 and NuRD are
recruited to cardiac loci. 3) Establish how the human Chd4 missense mutations lead to cardiac
disease.

## Key facts

- **NIH application ID:** 10452617
- **Project number:** 5R01HL156424-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Frank Leo Conlon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $536,739
- **Award type:** 5
- **Project period:** 2021-07-16 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452617

## Citation

> US National Institutes of Health, RePORTER application 10452617, Mechanism and Function of Cardiac Transcriptional Repression Networks (5R01HL156424-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10452617. Licensed CC0.

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