# Function and regulation of chromatin remodeling complexes in cardiac development and disease

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $555,179

## 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. Post-translational modifications of
histones act to regulate cardiac chromatin structure and hence, the temporal and
spatial program of gene regulation during cardiac development. We have found that
SMYD1, a cardiomyocyte essential histone methyltransferase interacts with the
chromatin remodeling MLL4 class of Complex of Proteins ASsociated with Set1
(COMPASS) complex. SMYD1 has been shown to be essential for cardiac
development and as we show here, causes CHD. Like SMYD1, two of the core
components of the MLL4-COMPASS complex, KMT2D/MLL4 and KDM6a are essential
for cardiac development and cause CHD. The goal of the current application is to test
the central hypothesis that SMYD1 acts within the MLL4-COMPASS complex to clear
histones at cardiac enhancers prior to gene activation. This will be achieved by: 1) 2)
Determining the function of SMYD1 in the assembly and function of the cardiac MLL4-
COMPASS complex and, 2) Establishing the requirement for KDM6a in MLL4-
COMPASS activity. Collectively, these studies will provide a detailed mechanistic
understanding of the tissue specific role for SMYD1 and MLL4-COMPASS complex in
cardiac development and heart disease.

## Key facts

- **NIH application ID:** 10906924
- **Project number:** 5R01HL165785-03
- **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:** 2024
- **Award amount:** $555,179
- **Award type:** 5
- **Project period:** 2022-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906924

## Citation

> US National Institutes of Health, RePORTER application 10906924, Function and regulation of chromatin remodeling complexes in cardiac development and disease (5R01HL165785-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10906924. Licensed CC0.

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