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CHD4 and SMYD1 repress common transcriptional programs in the developing heart
Wei Shi1, Lauren K Wasson2,3, Kerry M Dorr1
1Department of Biology and Genetics, McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.
Development (Cambridge, England)
|April 15, 2024
Summary
Chromatin regulator CHD4 interacts with SMYD1 in heart development. Together, they repress genes crucial for cardiac morphogenesis, revealing a new role for CHD4 in the developing heart.
Area of Science:
- Molecular Biology
- Developmental Biology
- Epigenetics
Background:
- Chromatin remodeling is vital for gene expression during development.
- The CHD4 protein is the core of the NuRD complex, known to repress transcription.
- The function of CHD4 in cardiomyocytes and its interactions within the heart remain unclear.
Purpose of the Study:
- To investigate the role of CHD4 in cardiomyocyte function and heart development.
- To identify novel protein interactions of CHD4 in the cardiac tissue.
- To elucidate the molecular mechanisms underlying CHD4 and SMYD1 function in cardiac gene regulation.
Main Methods:
- Quantitative proteomics to identify CHD4 interacting partners.
- Transcriptomic analysis (RNA-seq) of null embryonic mouse hearts.
- Chromatin accessibility assays (ATAC-seq) in null embryonic mouse hearts.
Main Results:
- CHD4 was found to interact with SMYD1, a muscle-specific histone methyltransferase.
- Loss of Smyd1 or Chd4 in embryonic mouse hearts led to repression of common genes.
- These repressed genes are involved in glycolysis, hypoxia response, and angiogenesis.
Conclusions:
- CHD4 plays a critical role in heart development through interaction with SMYD1.
- SMYD1 and CHD4 collaborate to repress key genes and pathways essential for cardiac morphogenesis.
- This study uncovers a novel mechanism for SMYD1 in repressing cardiac transcription during heart development.
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