Schematic representation of the classical class I, II and IV mammalian histone deacetylases (HDACs). Class I enzymes are homologous with the yeast, reduced potassium dependency-3 (Rpd3) and consist of HDAC1, 2, 3 and 8. The class II HDACs are homologous to the yeast, histone deacetylase-1 (Hda1) and enzymes in this class are further subdivided into two sub-classes. Class IIa is comprised of HDAC4, 5, 7 and 9; class IIb consists of HDAC6 and 10. The HDACs have a conserved deacetylase (DAC) domain depicted as a blue cylinder with the C- and N-terminal tails represented as black lines. Green cylinders represent the myocyte enhancer factor-2 (MEF2)-binding domains and short grey cylinders depict the 14-3-3 binding motifs with Ser phosphorylation sites. 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 [18].