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

Rusty L. Montgomery, Christopher A. Davis, Matthew J. Potthoff, Michael Haberland, Jens Fielitz, Xiaoxia Qi, Joseph A Hill, James A Richardson, Eric N Olson

Research output: Contribution to journalArticle

425 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1790-1802
Number of pages13
JournalGenes and Development
Volume21
Issue number14
DOIs
StatePublished - Jul 15 2007

Fingerprint

Histone Deacetylases
Morphogenesis
Gene Expression
Contractile Proteins
Organogenesis
Gene Deletion
Dilated Cardiomyopathy
Calcium Channels
Bradycardia
Growth
Cardiac Myocytes
Histones
Genes
Chromatin
Heart Ventricles
Hyperplasia
Tail
Cardiac Arrhythmias
Skeletal Muscle
Up-Regulation

Keywords

  • Heart development
  • Histone deacetylase
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Montgomery, R. L., Davis, C. A., Potthoff, M. J., Haberland, M., Fielitz, J., Qi, X., ... Olson, E. N. (2007). Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes and Development, 21(14), 1790-1802. https://doi.org/10.1101/gad.1563807

Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. / Montgomery, Rusty L.; Davis, Christopher A.; Potthoff, Matthew J.; Haberland, Michael; Fielitz, Jens; Qi, Xiaoxia; Hill, Joseph A; Richardson, James A; Olson, Eric N.

In: Genes and Development, Vol. 21, No. 14, 15.07.2007, p. 1790-1802.

Research output: Contribution to journalArticle

Montgomery RL, Davis CA, Potthoff MJ, Haberland M, Fielitz J, Qi X et al. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes and Development. 2007 Jul 15;21(14):1790-1802. https://doi.org/10.1101/gad.1563807
Montgomery, Rusty L. ; Davis, Christopher A. ; Potthoff, Matthew J. ; Haberland, Michael ; Fielitz, Jens ; Qi, Xiaoxia ; Hill, Joseph A ; Richardson, James A ; Olson, Eric N. / Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. In: Genes and Development. 2007 ; Vol. 21, No. 14. pp. 1790-1802.
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