Whitehouse Iestyn, Rando Oliver J, Delrow Jeff, Tsukiyama Toshio
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Nature. 2007 Dec 13;450(7172):1031-5. doi: 10.1038/nature06391.
Chromatin allows the eukaryotic cell to package its DNA efficiently. To understand how chromatin structure is controlled across the Saccharomyces cerevisiae genome, we have investigated the role of the ATP-dependent chromatin remodelling complex Isw2 in positioning nucleosomes. We find that Isw2 functions adjacent to promoter regions where it repositions nucleosomes at the interface between genic and intergenic sequences. Nucleosome repositioning by Isw2 is directional and results in increased nucleosome occupancy of the intergenic region. Loss of Isw2 activity leads to inappropriate transcription, resulting in the generation of both coding and noncoding transcripts. Here we show that Isw2 repositions nucleosomes to enforce directionality on transcription by preventing transcription initiation from cryptic sites. Our analyses reveal how chromatin is organized on a global scale and advance our understanding of how transcription is regulated.
染色质使真核细胞能够高效地包装其DNA。为了了解酿酒酵母基因组中染色质结构是如何被调控的，我们研究了ATP依赖的染色质重塑复合物Isw2在定位核小体中的作用。我们发现Isw2在启动子区域附近发挥作用，在基因序列和基因间序列的界面处重新定位核小体。Isw2介导的核小体重新定位具有方向性，并导致基因间区域核小体占有率增加。Isw2活性的丧失会导致不适当的转录，从而产生编码和非编码转录本。在这里，我们表明Isw2通过阻止从隐蔽位点起始转录来重新定位核小体，从而增强转录的方向性。我们的分析揭示了染色质在全局范围内是如何组织的，并加深了我们对转录调控方式的理解。
