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BET Bromodomains and P-TEFb in Cardiac Transcription and Heart Failure Pathogenesis

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Epigenetics in Cardiac Disease

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 1))

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Abstract

Stress-activated cardiac signaling cascades ultimately converge on defined transcriptional pathways that drive pathologic gene expression programs. Excessive or prolonged activation of these pathways culminates in hypertrophy, fibrosis, and contractile dysfunction. As the gene-regulatory machinery functions as a distal signal integrator in this disease process, defining mechanisms by which upstream pathways couple to chromatin-dependent signal transduction in cardiomyocytes (CMs) has been an area of intense scientific and therapeutic interest. It has long been recognized that dynamic positioning of acetyl-lysine on nucleosomal histone tails, regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes, plays a central role in cardiac plasticity and HF pathogenesis. In this chapter, we will discuss signaling events downstream of local chromatin acetylation in the heart and their role in pathologic cardiac plasticity and HF pathogenesis. We will highlight recently published studies that implicate BET family bromodomain-containing coactivator proteins as a critical link between activated cardiac enhancers, P-TEFb (positive transcription elongation factor b), and RNA polymerase II (Pol II) dynamics in the stressed myocardium.

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Funding

This work was funded by grants from the US National Institutes of Health (grants HL127240 and DK093821).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Gladstone Institute of Cardiovascular Disease and University of California, San Francisco School of Medicine, San Francisco, CA, USA

    Priti Anand & Saptarsi M. Haldar

  2. Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Amir Munir

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  2. Amir Munir
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Correspondence to Saptarsi M. Haldar .

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  1. Department of Molecular, Cardiology and Epigenetics, University of Heidelberg, Heidelberg, Germany

    Johannes Backs

  2. Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, CO, USA

    Timothy A. McKinsey

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Anand, P., Munir, A., Haldar, S.M. (2016). BET Bromodomains and P-TEFb in Cardiac Transcription and Heart Failure Pathogenesis. In: Backs, J., McKinsey, T.A. (eds) Epigenetics in Cardiac Disease. Cardiac and Vascular Biology, vol 1. Springer, Cham. https://doi.org/10.1007/978-3-319-41457-7_12

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