Three proteins define a class of human histone deacetylases related to yeast Hda1p
Three proteins define a class of human histone deacetylases related to yeast Hda1p
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DOI：
10.1073/pnas.96.9.4868
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发表时间：
1999-04-27
影响因子：
11.1
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Grozinger, CM;Hassig, CA;Schreiber, SL
基因表达部分受染色质重塑因子和核小体组蛋白乙酰化状态的调控，后者受组蛋白乙酰转移酶和组蛋白去乙酰化酶（HDAC）的调控，目前已鉴定出3种人HDAC酶和5种酵母HDAC酶，它们可分为两类：第一类以酵母Rpd 3-like蛋白为代表，第二类以酵母Hda 1-like蛋白为代表。人HDAC 1、HDAC 2和HDAC 3蛋白是第一类的成员，而尚未鉴定出II类人HDAC蛋白。利用Hda 1 p的氨基酸序列在GenBank/expressed sequence tag数据库中进行检索，从3个推测的II类人HDAC蛋白中克隆了部分序列，并将其命名为HDAC 4、HDAC 5和HDAC 6。这些蛋白具有I类人HDAC的保守催化结构域的某些特征，但也含有额外的序列结构域。有趣的是，HDAC 6包含两个催化结构域的内部复制，这两个催化结构域似乎彼此独立地发挥作用。这些II类HDAC蛋白在人体组织中具有差异mRNA表达，并具有体外HDAC活性，该活性可被阿司他汀A抑制。免疫共沉淀实验表明，这些HDAC蛋白不是先前鉴定的HDAC 1和HDAC 2 NRD和mSin 3A复合物的组分，然而，HDAC 4和HDAC 5在体内与HDAC 3缔合。这一发现表明，人类II类HDAC酶可能在不同于HDAC 1和HDAC 2的细胞过程中发挥作用。
Gene expression is in part controlled by chromatin remodeling factors and the acetylation state of nucleosomal histones, The latter process is regulated by histone acetyltransferases and histone deacetylases (HDACs), Previously, three human and five yeast HDAC enzymes had been identified, These can be categorized into two classes: the first class represented by yeast Rpd3-like proteins and the second by yeast Hda1-like proteins. Human HDAC1, HDAC2, and HDAC3 proteins are members of the first class, whereas no class II human HDAC proteins had been identified. The amino acid sequence of Hda1p was used to search the GenBank/expressed sequence tag databases to identify partial sequences from three putative class II human HDAC proteins, The corresponding full-length cDNAs were cloned and defined as HDAC4, HDAC5, and HDAC6, These proteins possess certain features present in the conserved catalytic domains of class I human HDACs, but also contain additional sequence domains. Interestingly, HDAC6 contains an internal duplication of two catalytic domains, which appear to function independently of each other. These class II HDAC proteins have differential mRNA expression in human tissues and possess in vitro HDAC activity that is inhibited by trichostatin A. Coimmunoprecipitation experiments indicate that these HDAC proteins are not components of the previously identified HDAC1 and HDAC2 NRD and mSin3A complexes, However, HDAC4 and HDAC5 associate with HDAC3 in vivo. This finding suggests that the human class II HDAC enzymes may function in cellular processes distinct from those of HDAC1 and HDAC2.