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Review

BET Protein-Mediated Transcriptional Regulation in Heart Failure

Division of Cardiology, Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
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Author to whom correspondence should be addressed.
Academic Editor: Ralph Knöll
Int. J. Mol. Sci. 2021, 22(11), 6059; https://doi.org/10.3390/ijms22116059
Received: 16 April 2021 / Revised: 29 May 2021 / Accepted: 1 June 2021 / Published: 4 June 2021
(This article belongs to the Special Issue Epigenetic Mechanisms of Cardiac Disease)
Heart failure is a complex disease process with underlying aberrations in neurohormonal systems that promote dysregulated cellular signaling and gene transcription. Over the past 10 years, the advent of small-molecule inhibitors that target transcriptional machinery has demonstrated the importance of the bromodomain and extraterminal (BET) family of epigenetic reader proteins in regulating gene transcription in multiple mouse models of cardiomyopathy. BETs bind to acetylated histone tails and transcription factors to integrate disparate stress signaling networks into a defined gene expression program. Under myocardial stress, BRD4, a BET family member, is recruited to superenhancers and promoter regions of inflammatory and profibrotic genes to promote transcription elongation. Whole-transcriptome analysis of BET-dependent gene networks suggests a major role of nuclear-factor kappa b and transforming growth factor-beta in the development of cardiac fibrosis and systolic dysfunction. Recent investigations also suggest a prominent role of BRD4 in maintaining cardiomyocyte mitochondrial respiration under basal conditions. In this review, we summarize the data from preclinical heart failure studies that explore the role of BET-regulated transcriptional mechanisms and delve into landmark studies that define BET bromodomain-independent processes involved in cardiac homeostasis. View Full-Text
Keywords: BET; BRD4; heart failure; dilated cardiomyopathy; phospholamban; chromatin remodeling; superenhancer; transcription regulation BET; BRD4; heart failure; dilated cardiomyopathy; phospholamban; chromatin remodeling; superenhancer; transcription regulation
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MDPI and ACS Style

Ijaz, T.; Burke, M.A. BET Protein-Mediated Transcriptional Regulation in Heart Failure. Int. J. Mol. Sci. 2021, 22, 6059. https://doi.org/10.3390/ijms22116059

AMA Style

Ijaz T, Burke MA. BET Protein-Mediated Transcriptional Regulation in Heart Failure. International Journal of Molecular Sciences. 2021; 22(11):6059. https://doi.org/10.3390/ijms22116059

Chicago/Turabian Style

Ijaz, Talha, and Michael A. Burke. 2021. "BET Protein-Mediated Transcriptional Regulation in Heart Failure" International Journal of Molecular Sciences 22, no. 11: 6059. https://doi.org/10.3390/ijms22116059

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