Histone Deacetylases in Cardiovascular Development and Disease

Bryan D. Young, Eric N. Olson

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

This chapter discusses the signal-responsive regulation that histone deacetylases (HDACs) provide to the cardiogenic and hypertrophic transcriptional pathways. The stimulatory effect of histone acetyltransferases (HATs) on gene expression is countered by the HDACs. The HDACs promote chromatin compaction, and thereby repress gene expression. In the myocyte, HATs and HDACs coordinately act as links between signal transduction pathways and the DNA-binding transcription factors that ultimately drive the gene programs of myogenic growth and differentiation. Eighteen human HDACs have been identified to date. They fall into three classes based on their homology, with three structurally and biochemically distinct yeast HDACs. Class I HDACs (1, 2, 3, 8 and 11) are related to yeast RPD3, class II HDACs (4, 5, 6, 7, 9 and 10) to yeast HDA1, and class III HDACs (Sirt1-7) to yeast Sir2. Class II HDACs are further divided into two subclasses, IIa (HDACs 4, 5, 7 and 9) and IIb (HDACs 6 and 10). In the remainder of this chapter, the term "class II HDACs" will refer specifically to the class IIa HDACs. Members of this subset (HDACs 4, 5, 7 and 9) have been shown to repress MEF2-mediated gene expression and myocyte growth. In contrast, increasing evidence suggests class I HDACs may be involved in promoting cellular growth. The class III HDACs, which act as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, have been implicated in the inhibition of cardiac hypertrophy and enhanced cardiomyocyte survival (Alcendor et al., 2004).

Original languageEnglish (US)
Title of host publicationHeart Development and Regeneration
PublisherElsevier Inc.
Pages715-727
Number of pages13
ISBN (Print)9780123813329
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Young, B. D., & Olson, E. N. (2010). Histone Deacetylases in Cardiovascular Development and Disease. In Heart Development and Regeneration (pp. 715-727). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-381332-9.00032-3