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Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
Published on: June 3, 2016
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Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease
Ralf Gilsbach1, Sebastian Preissl2, Björn A Grüning3
1Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany.
Nature Communications
|October 23, 2014
Summary
DNA methylation patterns in heart cells change significantly during development and in response to heart failure. These epigenetic changes in cardiomyocytes are closely linked to gene activity and cardiac function.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Molecular Cardiology
Background:
- The heart's phenotype is influenced by DNA methylation, but its role in cardiomyocytes is not fully understood.
- Understanding epigenetic regulation is crucial for comprehending heart development and disease.
Purpose of the Study:
- To investigate DNA methylation dynamics in cardiomyocytes during development and in heart failure.
- To correlate DNA methylation patterns with gene expression and cardiomyocyte function.
Main Methods:
- Generation and analysis of DNA methylomes from purified neonatal, adult healthy, and adult failing cardiomyocytes.
- Identification of differentially methylated genomic regions.
- Correlation analysis between DNA methylation, gene expression, and epigenetic marks (H3K27me3).
Main Results:
- Large genomic regions show differential methylation during cardiomyocyte maturation.
- Gene body demethylation strongly correlates with increased gene expression.
- De novo methylation by DNA methyltransferases 3A/B represses fetal cardiac genes, including sarcomeric components.
- Failing cardiomyocytes exhibit methylation patterns resembling neonatal cells.
Conclusions:
- DNA methylation is a dynamic epigenetic process in postnatal cardiomyocyte growth.
- Epigenetic modifications are tightly linked to gene regulation and cardiomyocyte activity during development and stress.
- Aberrant DNA methylation contributes to the pathophysiology of heart failure.
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