文章：

癌症生物学和NuRD:一个多面染色质重塑复合体

Cancer biology and NuRD: a multifaceted chromatin remodelling complex

原文发布日期：2011-07-07

DOI: 10.1038/nrc3091

类型: Review Article

开放获取: 否

要点：

1. The nucleosome remodelling and histone deacetylase (NuRD; also known as Mi-2) complex is a multisubunit chromatin remodelling complex that contains two core subunits (chromodomain-helicase-DNA-binding protein 3 (CHD3; also known as Mi-2α) and CHD4 (also known as Mi-2β), and histone deacetylase 1 (HDAC1) and HDAC2) with enzymatic functions. CHD3 and CHD4 catalyse ATP-dependent chromatin remodelling, and HDAC1 and HDAC2 mediate histone and protein deacetylation.
2. All subunits of the complex are encoded by multiple gene paralogues. Combinatorial assembly of these paralogues contributes to the targeting and function of the complex.
3. The metastasis-associated gene 1 (MTA1) subunit is widely overexpressed in many types of cancer and is associated with poor prognosis.
4. Unlike other chromatin remodelling complexes with well-defined roles in cancer, the NuRD complex can promote or suppress tumorigenesis depending on context.
5. NuRD complex recruitment to specific loci is mediated by multiple mechanisms, including recruitment by transcription factors and direct interaction with methylated DNA.
6. Emerging evidence suggests non-transcriptional roles of the NuRD complex in the maintenance of genome stability, including DNA replication, chromatin assembly and DNA repair.

要点翻译：

1. 核小体重塑和组蛋白去乙酰化酶复合体（NuRD，亦称Mi-2）是一种多亚基染色质重塑复合体，其核心组分包含两个具有酶活功能的结构单元：染色质域解旋酶DNA结合蛋白3（CHD3，即Mi-2α）与CHD4（即Mi-2β），以及组蛋白去乙酰化酶1（HDAC1）和HDAC2。其中CHD3与CHD4催化ATP依赖的染色质重塑过程，而HDAC1和HDAC2介导组蛋白及蛋白质的去乙酰化作用。
2. 该复合体所有亚基均由多旁系同源基因编码，这些同源基因的组合式组装决定了复合体的靶向特异性与功能定位。
3. 转移相关基因1（MTA1）亚基在多种恶性肿瘤中广泛过表达，且与不良预后密切相关。
4. 与其他在癌症中作用明确的染色质重塑复合体不同，NuRD复合体在不同微环境中既能促进亦可抑制肿瘤发生。
5. NuRD复合体通过多种机制被招募至特定基因组位点，包括转录因子介导的招募及与甲基化DNA的直接相互作用。
6. 最新研究表明，NuRD复合体在基因组稳定性维持中发挥着非转录调控功能，涉及DNA复制、染色质组装及DNA修复等重要生物学过程。

英文摘要：

The nucleosome remodelling and histone deacetylase (NuRD; also known as Mi-2) complex regulates gene expression at the level of chromatin. The NuRD complex has been identified — using both genetic and molecular analyses — as a key determinant of differentiation in mouse embryonic stem cells and during development in various model systems. Similar to other chromatin remodellers, such as SWI/SNF and Polycomb complexes, NuRD has also been implicated in the regulation of transcriptional events that are integral to oncogenesis and cancer progression. Emerging molecular details regarding the recruitment of NuRD to specific loci during development, and the modulation of these events in cancer, are used to illustrate how the inappropriate localization of the complex could contribute to tumour biology.

摘要翻译： 

核小体重塑与组蛋白去乙酰化酶（NuRD；亦称为Mi-2）复合物在染色质层面调控基因表达。通过遗传与分子分析，NuRD复合物已被确认为小鼠胚胎干细胞分化及多种模型系统发育过程中的关键决定因子。与其他染色质重塑因子（如SWI/SNF和Polycomb复合物）相似，NuRD亦参与调控与肿瘤发生及癌症进展密切相关的转录事件。最新揭示的分子细节显示，NuRD在发育过程中被招募至特定基因座，且这些事件在癌症中可被调控，用以说明该复合物不当定位如何促进肿瘤生物学。

原文链接：

Cancer biology and NuRD: a multifaceted chromatin remodelling complex