Table 1.

Histone deacetylases classification.

Class		Members	Localization	Description
Class I		HDAC1 HDAC2 HDAC3 HDAC8	nucleus nucleus nucleus primarily nucleus/cytoplasm	– most closely related to the yeast (Saccharomyces cerevisiae) transcriptional regulator Rpd3; – they have Zn2+ dependent catalytic domain; – contains the arginase-like amidino hydrolases; – ubiquitously expressed in most cell types; – about 370–500 amino acids; – HDAC1-3 possess low enzymatic activities when in isolation; – they may exist in multi-protein repressor complexes in the nucleus which increase their activity, for instance: SIN3/HDAC corepressor complex, NuRD, CoREST, NODE, SHIP1; – HDAC8 is not related with any multi-protein complex, involved in transcriptional repression; – HDACs of these class are very important in regulation of proliferation and in DNA damage response;
Class II	II A II B	HDAC4 HDAC5 HDAC7 HDAC9 HDAC6 HDAC10	nucleus/cytoplasm nucleus/cytoplasm nucleus/cytoplasm nucleus/cytoplasm primarily cytoplasm primarily cytoplasm	– class II is divided into two subclasses: IIA and IIB; – most closely related to the yeast (Saccharomyces cerevisiae) deacetylase Hda1; – they have Zn2+ dependent catalytic domain; – contains the arginase-like amidino hydrolases; – expression restricted to specific tissues; – about 1000 amino acids; – class II alone have little or no deacetylase activity; – may exist in large protein complexes as, for instance: HDAC–MEF2 complex, N-CoR, SMRT and BCoR; – catalytic domains is located in the COOH terminus of the peptide (exception: HDAC6—contains an internal duplication of two deacetylase catalytic domains); – HDAC7 possesses three repression domains; – HDAC9–many isoforms;
Class III/SIR2		SIRT1 SIRT2 SIRT3 SIRT4 SIRT5 SIRT6 SIRT7	nucleus/cytoplasm nucleus/cytoplasm nucleus/mitochondria mitochondria mitochondria nucleus nucleolus	– belongs to deoxyhypusine synthase (DHS)-like NAD/FAD-binding domain superfamily; – related to the yeast silencing protein Sir2 (Silent information regulator 2); – SIRT1–6 dependent on NAD+ for enzymatic activity; – SIRT7 contains putative enzymatic domain; – from 310 (SIRT4) to 747 (SIRT1) amino acids;
Class IV		HDAC11	nucleus/cytoplasm	– contains conserved residues in the catalytic core regions shared by both class I and II of HDACs; – have Zn2+ dependent catalytic domain; – contains the arginase-like amidino hydrolases; – lack of Nuclear Localization Signal (NLS); – 347 amino acids; – expression: kidney, heart, brain, skeletal muscle and testis; – HDAC11 is implicated in immune system regulation via regulation interleukin-10 expression