Circulation Research. 2006;98:15-24
doi: 10.1161/01.RES.0000197782.21444.8f
doi: 10.1161/01.RES.0000197782.21444.8f
© 2006 American Heart Association, Inc.
Reviews |
Control of Cardiac Growth by Histone Acetylation/Deacetylation
From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas.
Correspondence to E.N. Olson, University of Texas Southwestern Medical Center at Dallas, Department of Molecular Biology, 5323 Harry Hines Blvd, Dallas, TX 75390-9148. E-mail eric.olson{at}utsouthwestern.edu
This Review is part of a thematic series on New Paradigms of Transcriptional Control of Myocardial and Vascular Growth, which includes the following articles:
Redox-Dependent Transcriptional Regulation
Control of Cardiac Growth by Histone Acetylation/Deacetylation
Excitation-Transcription Coupling in Vascular Smooth Muscle
Gordon F. Tomaselli Editor
Histones control gene expression by modulating the structure of chromatin and the accessibility of regulatory DNA sequences to transcriptional activators and repressors. Posttranslational modifications of histones have been proposed to establish a "code" that determines patterns of cellular gene expression. Acetylation of histones by histone acetyltransferases stimulates gene expression by relaxing chromatin structure, allowing access of transcription factors to DNA, whereas deacetylation of histones by histone deacetylases promotes chromatin condensation and transcriptional repression. Recent studies demonstrate histone acetylation/deacetylation to be a nodal point for the control of cardiac growth and gene expression in response to acute and chronic stress stimuli. These findings suggest novel strategies for "transcriptional therapies" to control cardiac gene expression and function. Manipulation of histone modifying enzymes and the signaling pathways that impinge on them in the settings of pathological cardiac growth, remodeling, and heart failure represents an auspicious therapeutic approach.
Key Words: cardiac hypertrophy • histone acetyltransferase • histone deacetylase • gene expression • epigenetics
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