A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p
A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p
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DOI：
10.1074/jbc.274.17.11713
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发表时间：
1999-04-23
影响因子：
4.8
通讯作者：
Verdin, E
中科院分区：
文献类型：
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作者：
Fischle, W;Emiliani, S;Verdin, E
组蛋白脱乙酰酶是多蛋白复合体的催化亚单位，通过与序列特异的DNA结合因子相互作用，靶向特定的蛋白。我们克隆并鉴定了一个与酵母HDA1家族的组蛋白脱乙酰基酶同源的新的人类基因HDAC-A。对预测的HDAC-A的氨基酸序列进行分析，发现一个由967个氨基酸组成的开放阅读框架，包含两个结构域：一个与已知蛋白质没有同源性的NH2末端结构域和一个与已知组蛋白脱乙酰酶同源的COOH-末端结构域(与RPD3相似42%，与HDA1相似60%)，在序列数据库中另外发现了三个与HDAC-A高度同源的人cDNA，表明HDAC-A本身是一个新的人类组蛋白脱乙酰基酶家族的成员。编码HDAC-A的mRNA在多种人体组织中差异表达。表达的蛋白HDAC-AP具有组蛋白脱乙酰基酶活性，该活性定位于与HDA1p同源的COOH末端区域(氨基酸495-967)。在免疫沉淀实验中，HDAC-A与几种细胞蛋白特异地相互作用，表明它可能是一个更大的多蛋白复合体的一部分。
Histone deacetylases are the catalytic subunits of multiprotein complexes that are targeted to specific pro meters through their interaction with sequence-specific DNA-binding factors. We have cloned and characterized a new human cDNA, HDAC-A, with homology to the yeast HDA1 family of histone deacetylases. Analysis of the predicted amino acid sequence of HDAC-A revealed an open reading frame of 967 amino acids containing two domains: a NH2-terminal domain with no homology to known proteins and a COOH-terminal domain with homology to known histone deacetylases (42% similarity to RPD3, 60% similarity to HDA1), Three additional human cDNAs with high homology to HDAC-A were identified in sequence data bases, indicating that HDAC-A itself is a member of a new family of human histone deacetylases. The mRNA encoding HDAC-A was differentially expressed in a variety of human tissues. The expressed protein, HDAC-Ap, exhibited histone deacetylase activity and this activity mapped to the COOH-terminal region (amino acids 495-967) with homology to HDA1p, in immunoprecipitation experiments, HDAC-A interacted specifically with several cellular proteins, indicating that it might be part of a larger multiprotein complex.