BET-ting on chromatin-based therapeutics for heart failure.
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.
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA. Electronic address: saptarsi.haldar@case.edu.
Saptarsi M
SM
Haldar
Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: timothy.mckinsey@ucdenver.edu.
Timothy A
TA
McKinsey
D006332:Cardiomegaly / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000187:drug effects*; D044127:Epigenesis, Genetic; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
D002316:Cardiotonic Agents; D018797:Cell Cycle Proteins; D002843:Chromatin; D009687:Nuclear Proteins; D042925:Positive Transcriptional Elongation Factor B; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C479740:BCL11B protein, human; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C476123:HEXIM1 protein, human
BET proteins; Cardiac hypertrophy; Chromatin; Epigenetics; Heart failure; Transcription