Overview of the Classical Histone Deacetylase Enzymes and Histone Deacetylase Inhibitors

Figure 1

Evolutionary relationship between the classical histone deacetylase enzymes (HDACs). The HDAC superfamily form evolutionary distinct groups according to their sequence homology to yeast. Class I enzymes share similarity with the yeast, reduced potassium dependency-3 (Rpd3), and consist of HDAC1, 2, 3, and 8. Rpd3 is most homologous to HDAC1 and HDAC2. The class II HDACs share homology to the yeast, histone deacetylase-1 (Hda1), and enzymes in this class form two separate subclasses. Class IIa is comprised of HDAC4, 5, 7, and 9; class IIb consists of HDAC6 and 10. Hda1 is most closely related to HDAC6. The phylogenetic tree shows that HDAC11 does not share enough homology with class I or class II HDACs so forms class IV and shares some identity to both Rpd3 and Hda1. The percentage of HDAC amino acid sequence identity/similarity to that of Rpd3 or Hda1 is shown in brackets, for HDAC11 the sequence identity/similarity to Hda1 is shown and to Rpd3 is given in brackets. The HDACs have a conserved deacetylase (DAC) domain with the C- and N-terminal tails represented as black lines. Nuclear localization signals, the myocyte enhancer factor-2- (MEF2-) binding domains, and the 14-3-3 chaperone-binding motifs with serine phosphorylation sites are shown. The number of amino acid residues of the longest isoform of each HDAC is shown on the right, and the chromosomal site of each HDAC is shown in brackets. H. sapiens: Homo sapiens; S. cerevisiae: Saccharomyces cerevisiae; SE14: Ser-Glu-containing tetradecapeptide repeats; ZnF: ubiquitin-binding zinc finger domain. Adapted from [9–11].