Whitehouse I, Flaus A, Cairns B R, White M F, Workman J L, Owen-Hughes T
Division of Gene Regulation, University of Dundee, UK.
Nature. 1999 Aug 19;400(6746):784-7. doi: 10.1038/23506.
The generation of a local chromatin topology conducive to transcription is a key step in gene regulation. The yeast SWI/SNF complex is the founding member of a family of ATP-dependent remodelling activities capable of altering chromatin structure both in vitro and in vivo. Despite its importance, the pathway by which the SWI/SNF complex disrupts chromatin structure is unknown. Here we use a model system to demonstrate that the yeast SWI/SNF complex can reposition nucleosomes in an ATP-dependent reaction that favours attachment of the histone octamer to an acceptor site on the same molecule of DNA (in cis). We show that SWI/SNF-mediated displacement of the histone octamer is effectively blocked by a barrier introduced into the DNA, suggesting that this redistribution involves sliding or tracking of nucleosomes along DNA, and that it is achieved by a catalytic mechanism. We conclude that SWI/SNF catalyses the redistribution of nucleosomes along DNA in cis, which may represent a general mechanism by which ATP-dependent chromatin remodelling occurs.
生成有利于转录的局部染色质拓扑结构是基因调控的关键步骤。酵母SWI/SNF复合物是一类依赖ATP的重塑活性家族的创始成员,该家族能够在体外和体内改变染色质结构。尽管其很重要,但SWI/SNF复合物破坏染色质结构的途径尚不清楚。在这里,我们使用一个模型系统来证明酵母SWI/SNF复合物可以在依赖ATP的反应中重新定位核小体,该反应有利于组蛋白八聚体附着到同一DNA分子(顺式)上的受体位点。我们表明,DNA中引入的屏障有效地阻断了SWI/SNF介导的组蛋白八聚体的置换,这表明这种重新分布涉及核小体沿DNA的滑动或追踪,并且它是通过催化机制实现的。我们得出结论,SWI/SNF催化核小体在顺式中沿DNA的重新分布,这可能代表了依赖ATP的染色质重塑发生的一般机制。