Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility.

By Rusty L. Montgomery, C. Davis, Matthew J. Potthoff, M. Haberland, J. Fielitz, X. Qi, Joseph A. Hill, J. Richardson, E. Olson. Genes & Development, 2007

757 citations recorded by the source corpus.

Histone deacetylases (HDACs) tighten chromatin structure and repress gene expression through the removal of acetyl groups from histone tails. The class I HDACs, HDAC1 and HDAC2, are expressed ubiquitously, but their potential roles in tissue-specific gene expression and organogenesis have not been defined. To explore the functions of HDAC1 and HDAC2 in vivo, we generated mice with conditional null alleles of both genes. Whereas global deletion of HDAC1 results in death by embryonic day 9.5, mice lacking HDAC2 survive until the perinatal period, when they succumb to a spectrum of cardiac defects, including obliteration of the lumen of the right ventricle, excessive hyperplasia and apoptosis of cardiomyocytes, and bradycardia. Cardiac-specific deletion of either HDAC1 or HDAC2 does not evoke a phenotype, whereas cardiac-specific deletion of both genes results in neonatal lethality, accompanied by cardiac arrhythmias, dilated cardiomyopathy, and up-regulation of genes encoding skeletal muscle-specific contractile proteins and calcium channels. Our results reveal cell-autonomous and non-cell-autonomous functions for HDAC1 and HDAC2 in the control of myocardial growth, morphogenesis, and contractility, which reflect partially redundant roles of these enzymes in tissue-specific transcriptional repression.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/304388303329e773f9513a2a10fdae91fdfc8877

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Citations in the corpus

The developmental genetics of congenital heart disease (2008, background): “With regard to the heart, histone deacetylases have mostly been characterized as having a role in hypertrophy, but they are also important in heart developmen”
The world of protein acetylation. (2016, background): “HDAC2-null mice have severe cardiac malformations, bradycardia and die within the first 24 h of birth [290].”
Histone Deacetylase Inhibitors as Anticancer Drugs (2017, neutral): “ACNA2D2 HDAC1 or HDAC2 mutated C57BL/6 mice / [107]”
microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. (2008, methodology): “Gene Ontology analysis was performed as described previously (Montgomery et al. 2007).”
The many roles of histone deacetylases in development and physiology: implications for disease and therapy (2009, background): “It should be noted, however, that deletion or inhibition of HDACs often results in the upregulation or downregulation of approximately equivalent percentages of gene”