Classes of HDACs in Higher Eukaryotes
HDACs, are classified in four classes depending on sequence identity and domain organization:
| Class | Members | Catalytic sites | Subcellular localization | Tissue distribution | Substrates | Binding partners | Knockout phenotype |
|---|---|---|---|---|---|---|---|
| I | HDAC1 | 1 | Nucleus | Ubiquitous | Androgen receptor, SHP, p53, MyoD, E2F1, STAT3 | – | embryonic lethal, increased histone acetylation, increase in p21 and p27 |
| HDAC2 | 1 | Nucleus | Ubiquitous | Glucocorticoid receptor, YY1, BCL6, STAT3 | – | Cardiac defect | |
| HDAC3 | 1 | Nucleus | Ubiquitous | SHP, YY1, GATA1, RELA, STAT3, MEF2D | – | – | |
| HDAC8 | 1 | Nucleus | Ubiquitous? | – | EST1B | – | |
| IIA | HDAC4 | 1 | Nucleus / cytoplasm | heart, skeletal muscle, brain | GCMA, GATA1, HP1 | RFXANK | Defects in chondrocyte differentiation |
| HDAC5 | 1 | Nucleus / cytoplasm | heart, skeletal muscle, brain | GCMA, SMAD7, HP1 | REA, estrogen receptor | Cardiac defect | |
| HDAC7 | 1 | Nucleus / cytoplasm / mitochondria | heart, skeletal muscle, pancreas, placenta | PLAG1, PLAG2 | HIF1A, BCL6, endothelin receptor, ACTN1, ACTN4, androgen receptor, Tip60 | Maintenance of vascular integrity, increase in MMP10 | |
| HDAC9 | 1 | Nucleus / cytoplasm | brain, skeletal muscle | – | FOXP3 | Cardiac defect | |
| IIB | HDAC6 | 2 | Mostly cytoplasm | heart, liver, kidney, placenta | α-Tubulin, HSP90, SHP, SMAD7 | RUNX2 | – |
| HDAC10 | 1 | Mostly cytoplasm | liver, spleen, kidney | – | – | – | |
| III | sirtuins in mammals (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, SIRT7) | – | – | – | – | – | – |
| Sir2 in the yeast S. cerevisiae | – | – | – | – | – | – | |
| IV | HDAC11 | 2 | Nucleus / cytoplasm | brain, heart, skeletal muscle, kidney | – | – | – |
HDAC (except class III) contain zinc and are known as Zn-dependent histone deacetylases.
Read more about this topic: Histone Deacetylase
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