title: Isolation and characterization of a novel class II histone deacetylase, HDAC10.
abstract: A novel histone deacetylase, HDAC10, was isolated from a mixed tissue human cDNA library. HDAC10 was classified as a class II subfamily member based upon similarity to HDAC6. The genomic structure of HDAC10 was found to consist of 20 exons. HDAC10 has two sequence variants, HDAC10v1 and HDAC10v2, and two transcripts were detectable by Northern blot analysis. HDAC10v1 and HDAC10v2 were found to be identical through exon 17 but diverged after this exon. HDAC10v2 has an 82-bp alternate exon that generates a frameshift and shortens the sequence by 11 amino acids. In this study, the characterization of HDAC10v1 was performed. HDAC10v1 has an N-terminal catalytic domain, two putative C-terminal retinoblastoma protein binding domains, and a nuclear hormone receptor binding motif. The HDAC10v1 enzyme was found to be catalytically active based upon its ability to deacetylate a (3)H-acetylated histone H4 N-terminal peptide. Immunofluorescence detection of transfected HDAC10v1-FLAG indicated that the enzyme is a nuclear protein. Furthermore, coimmunoprecipitation experiments indicated that HDAC10v1 associated with HDAC2 and SMRT (silencing mediator for retinoid and thyroid hormone receptors). In addition, based upon the public data base, a single nucleotide polymorphism was found in the C terminus of HDAC10 which changes a Gly residue to Cys, suggesting that HDAC10 molecules containing these single nucleotide polymorphisms may be folded improperly. HDAC10 extends the HDAC superfamily and adds to a growing number of HDACs that have been found to have splice variants, suggesting that RNA processing may play a role in mediating the activity of HDACs.
authors.affiliation: Department of Functional Genomics, Novartis Pharmaceuticals, Summit, New Jersey 07901, USA.
authors.forename: Denise D
authors.initials: DD
authors.lastname: Fischer
authors.forename: Richard
authors.initials: R
authors.lastname: Cai
authors.forename: Umesh
authors.initials: U
authors.lastname: Bhatia
authors.forename: Fred A M
authors.initials: FA
authors.lastname: Asselbergs
authors.forename: Chuanzheng
authors.initials: C
authors.lastname: Song
authors.forename: Robert
authors.initials: R
authors.lastname: Terry
authors.forename: Nancy
authors.initials: N
authors.lastname: Trogani
authors.forename: Roland
authors.initials: R
authors.lastname: Widmer
authors.forename: Peter
authors.initials: P
authors.lastname: Atadja
authors.forename: Dalia
authors.initials: D
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D020134:Catalytic Domain; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015723:Gene Library; D014644:Genetic Variation; D006655:Histone Deacetylases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; C447828:HDAC10 protein, human; D006655:Histone Deacetylases