Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation
Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation
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DOI：
10.1101/gad.13.15.1924
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发表时间：
1999-08-01
影响因子：
10.5
通讯作者：
Reinberg, D
中科院分区：
文献类型：
--
作者：
Zhang, Y;Ng, HH;Reinberg, D
ATP 依赖性核小体重塑和核心组蛋白乙酰化和脱乙酰化代表了改变核小体结构的机制。 NuRD 是一种多亚基复合物，含有核小体重塑和组蛋白脱乙酰酶活性。组蛋白脱乙酰酶 HDAC1 和 HDAC2 以及组蛋白结合蛋白 RbAp48 和 RbAp46 形成 NuRD 和 Sin3-组蛋白脱乙酰酶复合物之间共享的核心复合物。核心复合物的组蛋白脱乙酰酶活性严重受损。一种与转移相关蛋白 1 MTA2 和含有甲基 CpG 结合结构域的蛋白 MBD3 高度相关的新型多肽被发现是 NuRD 复合物的亚基。 MTA2 调节组蛋白脱乙酰酶核心复合物的酶活性。 MBD3 介导 MTA2 与核心组蛋白脱乙酰酶复合物的结合。 MBD3 不直接结合甲基化 DNA，但与 MBD2（一种结合甲基化 DNA 的多肽）高度相关。据报道具有去甲基酶活性。 MBD2 与 NuRD 复合物相互作用，并将复合物引导至甲基化 DNA。 NuRD 可能提供一种通过 DNA 甲基化进行基因沉默的方法。
ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA. and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation.