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.