Table 1.
Parameter | Class I | Class IIa | Class IIb | Class III and IV |
---|---|---|---|---|
Yeast HDAC | RPD3 | HDA1 | HDA1 | SirT2 |
Human HDAC | HDAC-1–3, -8 | HDAC-4, -5, -7, -9 | HDAC-6, -10 | SirT1–7, HDAC-11 |
Molecular weight (kDa) |
– | 120–135 | 120–135 | 40–50 kDa |
Size (no. of amino acid residues) |
HDAC-1 (483), HDAC-2 (488), HDAC-3 (428), HDAC-8 (377) |
HDAC-4 (1084), HDAC-5 (1122), HDAC-7 (855), HDAC-9 (1011) |
HDAC-6 (1215), HDAC-10 (669) |
HDAC-11 (347) |
Distribution | Ubiquitous | Brain, heart | Testis, liver, kidney | Unknown |
Localization | Nuclear | Nuclear/ cytoplasmic |
Mostly cytoplasmic | Nuclear |
Chromosomal localization |
HDAC-1 (1p34.1), HDAC-2 (6q21), HDAC-3 (5q31), HDAC-8 (Xq13) |
HDAC-4 (2q37.2), HDAC-5 (17q21), HDAC-7 (12q13), HDAC-9 (7p21-p15) |
HDAC-6 (Xp11.22–23), HDAC-10 (22q13.31-q13.33) |
HDAC-11 (3p25.2) |
Target substrates |
Histones, p53, NF-κB |
Histones | Histones, tubulin, Hsp |
Histones, tubulin p53, TAF |
Catalytic sites | One | One | HDAC-6, two and HDAC-10, two |
Two |
Protein complexes |
NuRD, SIN3 | – | – | – |
Co-repressor | N-CoR, SMRT | N-CoR, SMRT | – | – |
Interacting proteins |
Rb, p53, MyoD, NF-κB, SP11, BRCA1, DNMT1, DNMT3A-B, MBD2–3, MECP2, ATM |
MEF2 | Tubulin, Hsp | p53 |
Co-factor | Zn | Zn | Zn | NAD+ |
Knockout phenotype |
HDAC-1, embryonic lethal, increased histone acetylation, increase in p21 and p27, HDAC-2, cardiac defect |
HDAC-4, defects in chondrocyte differentiation HDAC-5 and -9, cardiac defect HDAC-7, maintenance of vascular integrity, increase in MMP10 |
– | – |
Cellular function |
Participate in Sin3, NuRD, Co-REST complex (HDAC-1, -2); participate in SMRT/N-CoR (HDAC-3) |
Interaction with SMRT/N-CoR and the co-repressors BcoR and CtBP (HDAC-4) |
Tubulin deacetylase (HDAC-6) Recruitment other HDACs (HDAC-10) |
Repression of p53 activity Regulate the 3′-end processing machinery of mRNA (SirT1 and SirT2) |
CtBP: Carboxyl-terminal binding protein; HDAC: Histone deacetylase; Hsp: Heat-shock protein; MEF: Myocyte enhancer factor; N-CoR: Nuclear receptor co-repressor; NF-κB: Nuclear factor-κB; Rb: Retinoblastoma protein; SMRT: Silencing mediator for retinoid and thyroid hormone receptor.