text: Activity of these HDACs can be affected by phosphorylation. An increased amount of phosphorylation (hyperphosphorylation) leads to increased deacetylase activity, but degrades complex formation between HDACs 1 and 2 and between HDAC1 and mSin3A/YY1. A lower than normal amount of phosphorylation (hypophosphorylation) leads to a decrease in the amount of deacetylase activity, but increases the amount of complex formation. Mutation studies found that major phosphorylation happens at residues Ser421 and Ser423. Indeed, when these residues were mutated, a drastic reduction was seen in the amount of deacetylation activity. This difference in the state of phosphorylation is a way of keeping an optimal level of phosphorylation to ensure there is no over or under expression of deacetylation. HDACs 1 and 2 have been found only exclusively in the nucleus. In HDAC1 knockout (KO) mice, mice were found to die during embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase Inhibitors (CDKIs) p21 and p27. Not even upregulation of the other Class I HDACs could compensate for the loss of HDAC1. This inability to recover from HDAC1 KO leads researchers to believe that there are both functional uniqueness to each HDAC as well as regulatory cross-talk between factors.
  HDAC3
  HDAC3 has been found to be most closely related to HDAC8. HDAC3 contains a non-conserved region in the C-terminal region that was found to be required for transcriptional repression as well as its deacetylase activity. It also contains two regions, one called a Nuclear Localization Signal (NLS) as well as a Nuclear Export Signal (NES). The NLS functions as a signal for nuclear action while an NES functions with HDACs that perform work outside of the nucleus. A presence of both signals for HDAC3 suggests it travels between the nucleus and the cytoplasm. HDAC3 has even been found to interact with the plasma membrane. Silencing Mediator for Retinoic Acid and Thyroid Hormone (SMRT) receptors and Nuclear Receptor Co-Repressor (N-CoR) factors must be utilized by HDAC3 in order to activate it. Upon doing so, it gains the ability to co-precipitate with HDACs 4, 5, and 7. HDAC3 can also be found complexed together with HDAC-related protein (HDRP). HDACs 1 and 3 have been found to mediate Rb-RbAp48 interactions which suggests that it functions in cell cycle progression. HDAC3 also shows involvement in stem cell self-renewal and a transcription independent role in mitosis.