BET-ting on chromatin-based therapeutics for heart failure

J Mol Cell Cardiol. 2014 Sep:74:98-102. doi: 10.1016/j.yjmcc.2014.05.002. Epub 2014 May 14.

Abstract

Studies of transcriptional mechanisms in heart failure have focused heavily on roles of sequence-specific DNA-binding factors such as NFAT, MEF2 and GATA4. Recent findings have illuminated crucial functions for epigenetic regulators in the control of cardiac structural remodeling and mechanical dysfunction in response to pathological stress. Here, we review the current understanding of chromatin-dependent signal transduction in cardiac gene control, and highlight the potential for pharmacologic regulation of BET acetyl-lysine binding proteins as a means of treating heart failure.

Keywords: BET proteins; Cardiac hypertrophy; Chromatin; Epigenetics; Heart failure; Transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiomegaly / drug therapy*
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology
  • Cardiotonic Agents / therapeutic use*
  • Cell Cycle Proteins
  • Chromatin / drug effects*
  • Epigenesis, Genetic*
  • Heart Failure / drug therapy*
  • Heart Failure / genetics
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Humans
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Positive Transcriptional Elongation Factor B / genetics
  • Positive Transcriptional Elongation Factor B / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • BCL11B protein, human
  • BRD4 protein, human
  • Cardiotonic Agents
  • Cell Cycle Proteins
  • Chromatin
  • HEXIM1 protein, human
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Positive Transcriptional Elongation Factor B