Class-I: Class I HDACs share homology with the yeast Rpd3. This class includes HDACs 1, 2, 3, and 8, and its members are expressed ubiquitously in humans. Members 1, 2, and 3 are found in multi-protein repressor complexes in the nucleus, where they regulate gene expression. HDAC8 is found in both the nucleus and cytoplasm, and while it has not been found in any multi-protein complexes, it has been described to be involved in transcriptional repression. (1)
Reference
1. Koeneke, E., Witt, O., & Oehme, I.HDAC Family Members Intertwined in the Regulation of Autophagy: A Druggable Vulnerability in Aggressive Tumor Entities. Cells.2015;4(2):135-168. PMID: 25915736.
Class-II: Class II HDACs share homology with yeast Hda1, and are sub-classified into Classes IIa and IIb. The former group contains HDACs 4, 5, 7, and 9, and HDACs 6 and 10 belong to group IIb. (1)
Class IIa HDACs shuttle between the nucleus and cytoplasm, This group of HDACs regulate the activity of transcription factors. Class IIb HDACs seem to have primarily cytoplasmic roles, with HDAC6 deacetylatingalpha-tubulin and functioning as part of protein aggresome formation and processing.
Reference
1. Koeneke, E., Witt, O., & Oehme, I.HDAC Family Members Intertwined in the Regulation of Autophagy: A Druggable Vulnerability in Aggressive Tumor Entities. Cells.2015;4(2):135-168. PMID: 25915736.
Class-IV: Class IV has a single member, HDAC11, whose structure bears some resemblance to Classes I and II HDACs, but is not similar enough to be placed in either class. The specific roles of HDAC11 are still being elucidated, but it is notable that its structure is evolutionarily conserved, not only in vertebrates and invertebrates, but also in plants. (1)
Reference
1. Koeneke, E., Witt, O., & Oehme, I.HDAC Family Members Intertwined in the Regulation of Autophagy: A Druggable Vulnerability in Aggressive Tumor Entities. Cells.2015;4(2):135-168. PMID: 25915736.
SIR2: Class III HDACs are sirtuin family enzymes. This class of proteins is related to the transcriptional repressor Sir2 (Silent information regulator 2) in the budding yeast. Yeast has five sirtuins including Sir2 and four homologs, Hst1-4 (Homolog of Sir two). The sirtuin deacetylases contain a conserved catalytic domain that is not related to deacetylase domain of other HDAC classes. Thus, the sirtuins catalyze deacetylation by a different mechanism that requires NAD+ as a cofactor. (1)
Reference
1. Jeon J. H., Lee Y. H.Histone acetylation in fungal pathogens of plants. Plant Pathol.J.2014;30(1):1-9. PMID: 25288980.
