Isolation and characterization of a novel class II histone deacetylase, HDAC10

被引:105
作者
Fischer, DD
Cai, R
Bhatia, U
Asselbergs, FAM
Song, CZ
Terry, R
Trogani, N
Widmer, R
Atadja, P
Cohen, D
机构
[1] Nova Pharmaceut Corp, Dept Funct Genom, Summit, NJ 07901 USA
[2] Nova Pharmaceut Corp, Dept Oncol, Summit, NJ 07901 USA
[3] Novartis Pharma AG, Dept Funct Genom, CH-4056 Basel, Switzerland
关键词
D O I
10.1074/jbc.M108055200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 MUM 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 BDAC10v1 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.
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页码:6656 / 6666
页数:11
相关论文
共 63 条
[1]   Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2 [J].
Afshar, G ;
Murnane, JP .
GENE, 1999, 234 (01) :161-168
[2]   Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression [J].
Alland, L ;
Muhle, R ;
Hou, H ;
Potes, J ;
Chin, L ;
SchreiberAgus, N ;
DePinho, RA .
NATURE, 1997, 387 (6628) :49-55
[3]   Nuclear hormone receptors and gene expression [J].
Aranda, A ;
Pascual, A .
PHYSIOLOGICAL REVIEWS, 2001, 81 (03) :1269-1304
[4]  
AUSUBEL FM, 1993, CURR PROTOCOLS MO S1, V23
[5]  
AUSUBEL FM, 1993, CURR PROTOCOLS MO S1, V26
[6]   Histone deacetylases: transcriptional repression with SINers and NuRDs [J].
Ayer, DE .
TRENDS IN CELL BIOLOGY, 1999, 9 (05) :193-198
[7]   Repulsive axon guidance: Abelson and enabled play opposing roles downstream of the roundabout receptor [J].
Bashaw, GJ ;
Kidd, T ;
Murray, D ;
Pawson, T ;
Goodman, CS .
CELL, 2000, 101 (07) :703-715
[8]   Pfam 3.1: 1313 multiple alignments and profile HMMs match the majority of proteins [J].
Bateman, A ;
Birney, E ;
Durbin, R ;
Eddy, SR ;
Finn, RD ;
Sonnhammer, ELL .
NUCLEIC ACIDS RESEARCH, 1999, 27 (01) :260-262
[9]   Genomewide studies of histone deacetylase function in yeast [J].
Bernstein, BE ;
Tong, JK ;
Schreiber, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (25) :13708-13713
[10]   Class II histone deacetylases: Structure, function, and regulation [J].
Bertos, NR ;
Wang, AH ;
Yang, XJ .
BIOCHEMISTRY AND CELL BIOLOGY, 2001, 79 (03) :243-252