NUCLEOSOME DISRUPTION AND ENHANCEMENT OF ACTIVATOR BINDING BY A HUMAN SW1/SNF COMPLEX
NUCLEOSOME DISRUPTION AND ENHANCEMENT OF ACTIVATOR BINDING BY A HUMAN SW1/SNF COMPLEX
复制标题
DOI：
10.1038/370477a0
复制
发表时间：
1994-08-11
期刊：
影响因子：
64.8
通讯作者：
GREEN, MR
中科院分区：
文献类型：
--
作者：
KWON, H;IMBALZANO, AN;GREEN, MR
染色质结构可以通过阻止序列特异性激活蛋白(激活物)进入其启动子结合部位来影响真核结构基因的转录活性(1)。例如，与裸露的DNA相比，酵母GAL4蛋白的DNA结合域与核小体核心的相互作用非常差(见下文)，而其他激活剂的结合受到更强的抑制(2，3)。因此，激活剂与核小体DNA结合的方式是转录激活的一个关键方面。遗传学研究表明，酿酒酵母的多组分SWI/SNF复合体通过改变染色质的结构来促进转录(4，5)。在这里，我们鉴定并部分纯化了酵母SWI/SNF复合体(hSWI/SNF复合体)的人类同源物。我们发现，部分纯化的hSWI/SNF复合体介导了对核小体的ATP依赖的破坏，从而使激活剂GAL4-VP16和GAL4-AH能够结合在核小体核心内。我们的结论是，hSWI/SNF复合体直接作用于染色质结构重组，从而促进转录因子的结合。
CHROMATIN structure can affect the transcriptional activity of eukaryotic structural genes by blocking access of sequence-specific activator proteins (activators) to their promoter-binding sites(1). For example, the DNA-binding domain of the yeast GAL4 protein interacts very poorly with nucleosome cores compared with naked DNA(2) (and see below), and binding of other activators is even more strongly inhibited(2,3). The way in which activators bind to nucleosomal DNA is therefore a critical aspect of transcriptional activation. Genetic studies have suggested that the multi-component SWI/SNF complex of Saccharomyces cerevisiae facilitates transcription by altering the structure of the chromatin(4,5). Here we identify and partially purify a human homologue of the yeast SWI/SNF complex (hSWI/SNF complex). We show that a partially purified hSWI/SNF complex mediates the ATP-dependent disruption of a nucleosome, thereby enabling the activators, GAL4-VP16 and GAL4-AH, to bind within a nucleosome core. We conclude that the hSWI/SNF complex acts directly to reorganize chromatin structure so as to facilitate binding of transcription factors.