Functional domains of histone deacetylase-3.
Post-translational modifications of histones, in general, and acetylation/deacetylation, in particular, can dramatically alter gene expression in eukaryotic cells. In humans, four highly homologous class I HDAC enzymes (HDAC1, HDAC2, HDAC3, and HDAC8) have been identified to date. Although HDAC3 shares some structural and functional similarities with other class I HDACs, it exists in multisubunit complexes separate and different from other known HDAC complexes, implying that individual HDACs might function in a distinct manner. In this current study, to understand further the cellular function of HDAC3 and to uncover possible unique roles this protein may have in gene regulation, we performed a detailed analysis of HDAC3 using deletion mutations. Surprisingly, we found that the non-conserved C-terminal region of HDAC3 is required for both deacetylase and transcriptional repression activity. In addition, we discovered that the central portion of the HDAC3 protein possesses a nuclear export signal, whereas the C-terminal part of HDAC3 contributes to the protein's localization in the nucleus. Finally, we found that HDAC3 forms oligomers in vitro and in vivo and that the N-terminal portion of HDAC3 is necessary for this property. These data indicate that HDAC3 comprises separate, non-overlapping domains that contribute to the unique properties and function of this protein.
Yang
Wen-Ming
WM
H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
Tsai
Shih-Chang
SC
Wen
Yu-Der
YD
Fejer
Gyorgy
G
Seto
Edward
E
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D019281:Dimerization; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000032:analysis / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D012097:Repressor Proteins / Q000502:physiology; D013329:Structure-Activity Relationship; D000099186:Histone Deacetylase 3
D006655:Histone Deacetylases; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3