对核小体重塑去乙酰化酶（NuRD）亚基的分析揭示了一种组蛋白去乙酰化酶核心复合物以及与DNA甲基化的联系。
Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.
作者信息
Zhang Y, Ng H H, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D
机构信息
Howard Hughes Medical Institute (HHMI), Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
出版信息
Genes Dev. 1999 Aug 1;13(15):1924-35. doi: 10.1101/gad.13.15.1924.
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.
ATP 依赖的核小体重塑以及核心组蛋白的乙酰化和去乙酰化代表了改变核小体结构的机制。核小体重塑去乙酰化酶复合物（NuRD）是一种包含核小体重塑和组蛋白去乙酰化酶活性的多亚基复合物。组蛋白去乙酰化酶 HDAC1 和 HDAC2 以及组蛋白结合蛋白 RbAp48 和 RbAp46 形成了 NuRD 和 Sin3 - 组蛋白去乙酰化酶复合物之间共享的核心复合物。核心复合物的组蛋白去乙酰化酶活性严重受损。一种与转移相关蛋白 1（MTA2）高度相关的新型多肽以及含甲基 - CpG 结合结构域的蛋白（MBD3）被发现是 NuRD 复合物的亚基。MTA2 调节组蛋白去乙酰化酶核心复合物的酶活性。MBD3 介导 MTA2 与核心组蛋白去乙酰化酶复合物的结合。MBD3 不直接结合甲基化 DNA，但与 MBD2 高度相关，MBD2 是一种能结合甲基化 DNA 且据报道具有去甲基化酶活性的多肽。MBD2 与 NuRD 复合物相互作用并将该复合物导向甲基化 DNA。NuRD 可能提供了一种通过 DNA 甲基化实现基因沉默的方式。
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