Identification of HDAC10, a novel class II human histone deacetylase containing a leucine-rich domain.
Histone acetylation is important for regulating chromatin structure and gene expression. Three classes of mammalian histone deacetylases have been identified. Among class II, there are five known members, namely HDAC4, HDAC5, HDAC6, HDAC7 and HDAC9. Here we describe the identification and characterization of a novel class II member termed HDAC10. It is a 669 residue polypeptide with a bipartite modular structure consisting of an N-terminal Hda1p-related putative deacetylase domain and a C-terminal leucine-rich domain. HDAC10 is widely expressed in adult human tissues and cultured mammalian cells. It is enriched in the cytoplasm and this enrichment is not sensitive to leptomycin B, a specific inhibitor known to block the nuclear export of other class II members. The leucine-rich domain of HDAC10 is responsible for its cytoplasmic enrichment. Recombinant HDAC10 protein possesses histone deacetylase activity, which is sensitive to trichostatin A, a specific inhibitor for known class I and class II histone deacetylases. When tethered to a promoter, HDAC10 is able to repress transcription. Furthermore, HDAC10 interacts with HDAC3 but not with HDAC4 or HDAC6. These results indicate that HDAC10 is a novel class II histone deacetylase possessing a unique leucine-rich domain.
Tong
Jenny J
JJ
Molecular Oncology Group, Department of Medicine, McGill University Health Center, 687 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.
Liu
Jianhong
J
Bertos
Nicholas R
NR
Yang
Xiang-Jiao
XJ
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D017930:Genes, Reporter; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012097:Repressor Proteins; C447828:HDAC10 protein, human; D006655:Histone Deacetylases; D007930:Leucine