Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1
Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1
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DOI：
10.1074/jbc.m007372200
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发表时间：
2001-03-02
影响因子：
4.8
通讯作者：
Howard, BH
中科院分区：
文献类型：
--
作者：
Humphrey, GW;Wang, YH;Howard, BH
人组蛋白去乙酰化酶I（HDAC1）和II（HDAC2）是同源蛋白（84%的同一性），它们催化从核心组蛋白修饰的N末端赖氨酸上释放乙酰基。在许多真核生物中，组蛋白去乙酰化与转录失活（即沉默）的瞬时和持久状态相关。在这项研究中，我们分析了含有HDAC1和HDAC2的复合物，以鉴定与这些去乙酰化酶最稳定结合的蛋白质。复合物cI（9.5S）含有转录辅阻遏物CoREST/kiaa0071和一种与FAD依赖的氧化还原酶同源的蛋白质kiaa0601。复合物cII（15S）含有不少于15种蛋白质，包括CHD3/4（Mi - 2）、Mta - L1、RbAp48/46和MBD3，这些是脊椎动物核小体重塑复合物的特征。在天然条件下，cI和cII可能含有HDAC1、HDAC2或两者都有；它们可以解离为仅含HDAC1或HDAC2的cI和cII核心复合物。（m）CpG结合蛋白MBD2仅与HDAC1 cII核心复合物相关。我们提出一个模型，其中HDAC1核心复合物可通过MBD2靶向甲基化DNA，并且通过形成HDAC1/2 cII二聚体招募HDAC2。我们注意到cI组分CoREST/kiaa0071和cII组分Mta - L1共享一个包含SANT结构域的同源区域；该结构域可能在复合物组装中起作用。
Human histone deacetylases I (HDAC1) and II (HDAC2) are homologous proteins (84% identity) that catalyze release of acetyl groups from modified N-terminal lysines of core histones, Histone deacetylation is correlated with both transient and persistent states of transcriptional inactivity (i.e. silencing) in many eukaryotes, In this study, we analyzed complexes containing HDAC1 and HDAC2 to identify the proteins most stably associated with these deacetylases. Complex cI (9.5 S) contained transcriptional corepressor CoREST/ kiaa0071 and a protein homologous to FAD-dependent oxidoreductases, kiaa0601, Complex cII (15 S) contained greater than or equal to 15 proteins, including CHD3/4 (Mi-2), Mta-L1, RbAp48/ 46, and MBD3, characteristic of vertebrate nucleosome-remodeling complexes. Under native conditions, cI and cII may contain HDAC1, HDAC2 or both; these can be dissociated to cI and cII core complexes containing only HDAC1 or HDAC2, The (m)CpG-binding protein MBD2 was associated only with the HDAC1 cII core complex, A model is proposed in which HDAC1 core complexes can be targeted to methylated DNA via MBD2 with recruitment of HDAC2 occurring through formation of HDAC1/2 cII dimers, We note that the cI component CoREST/kiaa0071 and the cII component Mta-L1 share a region of homology that includes a SANT domain; this domain may play a role in complex assembly.