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. HDAC8 HDAC8 has been found to be most similar to HDAC3. Its major feature is its catalytic domain which contains an NLS region in the center. Two transcripts of this HDAC have been found which include a 2.0kb transcript and a 2.4kb transcript. Unlike the other HDAC molecules, when purified, this HDAC showed to be enzymatically active. At this point, due to its recent discovery, it is not yet known if it is regulated by co-repressor protein complexes. Northern blots have revealed that different tissue types show varying degrees of HDAC8 expression but has been observed in smooth muscles and is thought to contribute to contractility. Class II HDACs Class IIA The Class IIA HDACs includes HDAC4, HDAC5, HDAC7 and HDAC9. HDACs 4 and 5 have been found to most closely resemble each other while HDAC7 maintains a resemblance to both of them. There have been three discovered variants of HDAC9 including HDAC9a, HDAC9b and HDAC9c/HDRP, while more have been suspected. The variants of HDAC9 have been found to have similarities to the rest of the Class IIA HDACs. For HDAC9, the splicing variants can be seen as a way of creating a "fine-tuned mechanism" for differentiation expression levels in the cell. Different cell types may take advantage and utilize different isoforms of the HDAC9 enzyme allowing for different forms of regulation. HDACs 4, 5 and 7 have their catalytic domains located in the C-terminus along with an NLS region while HDAC9 has its catalytic domain located in the N-terminus. However, the HDAC9 variant HDAC9c/HDRP lacks a catalytic domain but has a 50% similarity to the N-terminus of HDACs 4 and