Tong J K, Hassig C A, Schnitzler G R, Kingston R E, Schreiber S L
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature. 1998 Oct 29;395(6705):917-21. doi: 10.1038/27699.
The dynamic assembly and remodelling of eukaryotic chromosomes facilitate fundamental cellular processes such as DNA replication and gene transcription. The repeating unit of eukaryotic chromosomes is the nucleosome core, consisting of DNA wound about a defined octamer of histone proteins. Two enzymatic processes that regulate transcription by targeting elements of the nucleosome include ATP-dependent nucleosome remodelling and reversible histone acetylation. The histone deacetylases, however, are unable to deacetylate oligonucleosomal histones in vitro. The protein complexes that mediate ATP-dependent nucleosome remodelling and histone acetylation/deacetylation in the regulation of transcription were considered to be different, although it has recently been suggested that these activities might be coupled. We report here the identification and functional characterization of a novel ATP-dependent nucleosome remodelling activity that is part of an endogenous human histone deacetylase complex. This activity is derived from the CHD3 and CHD4 proteins which contain helicase/ATPase domains found in SWI2-related chromatin remodelling factors, and facilitates the deacetylation of oligonucleosomal histones in vitro. We refer to this complex as the nucleosome remodelling and deacetylating (NRD) complex. Our results establish a physical and functional link between the distinct chromatin-modifying activities of histone deacetylases and nucleosome remodelling proteins.
真核染色体的动态组装与重塑有助于DNA复制和基因转录等基本细胞过程。真核染色体的重复单元是核小体核心，它由缠绕在特定组蛋白八聚体上的DNA组成。通过靶向核小体元件来调节转录的两个酶促过程包括ATP依赖性核小体重塑和组蛋白可逆乙酰化。然而，组蛋白脱乙酰酶在体外无法使寡核小体组蛋白脱乙酰化。在转录调控中介导ATP依赖性核小体重塑和组蛋白乙酰化/脱乙酰化的蛋白质复合物被认为是不同的，尽管最近有人提出这些活性可能是相互关联的。我们在此报告了一种新型ATP依赖性核小体重塑活性的鉴定及其功能特征，该活性是内源性人类组蛋白脱乙酰酶复合物的一部分。这种活性源自CHD3和CHD4蛋白，它们含有在SWI2相关染色质重塑因子中发现的解旋酶/ATP酶结构域，并在体外促进寡核小体组蛋白的脱乙酰化。我们将这种复合物称为核小体重塑与脱乙酰化（NRD）复合物。我们的结果在组蛋白脱乙酰酶和核小体重塑蛋白不同的染色质修饰活性之间建立了物理和功能联系。
