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

  • Priti Anand
  • Amir Munir
  • Saptarsi M. HaldarEmail author
Chapter
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol.)

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.

Keywords

Cardiac Hypertrophy Transverse Aortic Constriction Pathologic Cardiac Hypertrophy Positive Transcription Elongation Factor Myocardial Gene Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Funding

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

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Gladstone Institute of Cardiovascular Disease and University of California, San Francisco School of MedicineSan FranciscoUSA
  2. 2.Case Western Reserve University School of MedicineClevelandUSA

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