Related Experiment Video
Updated: Dec 3, 2025
13:03
Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
Published on: June 3, 2016
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Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to
Soo Young Kim1, Xin Zhang2, Gabriele G Schiattarella1
1Division of Cardiology, Department of Internal Medicine (S.Y.K., G.G.S., F.A., K.M.F., N.J., P.A.S., H.I.M., X.L., L.I.S., S.L., T.G.G., J.A.H.), University of Texas Southwestern, Dallas.
Circulation
|October 28, 2020
Summary
Bromodomain and extraterminal (BET) protein BRD4 is essential for maintaining normal cardiac function. Loss of BRD4 in cardiomyocytes leads to dilated cardiomyopathy and disrupts mitochondrial energy production, highlighting its critical role in heart health.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Mitochondrial Physiology
Background:
- BET proteins, including BRD4, are therapeutic targets for cancer and cardiovascular diseases.
- Pharmacological inhibitors like JQ1 show promise in preclinical models of heart failure.
- Genetic validation of BRD4's role in the heart is lacking.
Purpose of the Study:
- To investigate the function of BRD4 in cardiac pathophysiology using a genetic approach.
- To elucidate the role of BRD4 in heart development and mature function.
- To validate findings from pharmacological BET inhibitor studies.
Main Methods:
- Generated a cardiomyocyte-specific BRD4 knockout mouse model.
- Performed comprehensive functional, transcriptomic, and mitochondrial analyses.
- Utilized computational analysis to identify regulatory transcription factors.
Main Results:
- BRD4 loss caused progressive decline in heart function, leading to dilated cardiomyopathy.
- Transcriptomic analysis revealed disruption of mitochondrial energy production genes.
- Mitochondrial studies confirmed altered electron transport chain activity.
- Estrogen-related receptor α was identified as a key regulator of BRD4-dependent genes.
Conclusions:
- BRD4 plays a critical, previously unrecognized role in cardiomyocyte mitochondrial homeostasis.
- BRD4 is indispensable for maintaining normal cardiac function.
- Genetic ablation of BRD4 has distinct and severe consequences compared to pharmacological inhibition.
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