Isolation and characterization of a novel class II histone deacetylase, HDAC10
Isolation and characterization of a novel class II histone deacetylase, HDAC10
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DOI：
10.1074/jbc.m108055200
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发表时间：
2002-02-22
影响因子：
4.8
通讯作者：
Cohen, D
中科院分区：
文献类型：
--
作者：
Fischer, DD;Cai, R;Cohen, D
从人混合组织cDNA文库中分离到一种新的组蛋白脱乙酰基酶HDAC10。根据与UM的相似性，HDAC10被归类为II类亚家族成员，其基因组结构由20个外显子组成。HDAC10有两个序列变体，即HDAC10v1和HDAC10v2，Northern杂交分析发现有两个转录本。通过外显子17发现HDAC10v1和HDAC10v2是相同的，但在该外显子之后发生了分化。HDAC10v2有一个82bp的交替外显子，可以产生移码，并将序列缩短11个氨基酸。在本研究中，对HDAC10v1进行了表征。HDAC10v1有一个N端催化结构域，两个假定的C端视网膜母细胞瘤蛋白结合域，以及一个核激素受体结合基序。BDAC10v1酶被发现具有催化活性，因为它能够脱乙酰化组蛋白H4N端肽。对HDAC10v1-FLAG的免疫荧光检测表明该酶为核蛋白。此外，免疫共沉淀实验表明，HDAC10v1与HDAC2和SMRT(视黄醇和甲状腺激素受体的沉默介质)有关。此外，基于公共数据库，单核苷酸多态。在HDAC10的C末端发现了一个将甘氨酸残基转变为半胱氨酸的基因，这表明含有这些单核苷酸多态的HDAC10分子可能被错误地折叠。HDAC10扩展了HDAC超家族，并增加了越来越多的具有剪接变体的HDAC，这表明RNA加工可能在调节HDAC的活性中发挥作用。
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.