Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet, Novum, Huddinge, Sweden.
EMBO J. 2010 Jul 7;29(13):2126-34. doi: 10.1038/emboj.2010.109. Epub 2010 Jun 4.
DNA topoisomerases regulate the topological state of the DNA double helix and are key enzymes in the processes of DNA replication, transcription and genome stability. Using the fission yeast model Schizosaccharomyces pombe, we investigate genome wide how DNA topoisomerases I and II affect chromatin dynamics and gene expression in vivo. We show that topoisomerase I activity is directly required for efficient nucleosome disassembly at gene promoter regions. Lack of topoisomerase activity results in increased nucleosome occupancy, perturbed histone modifications and reduced transcription from these promoters. Strong correlative evidence suggests that topoisomerase I cooperates with the ATP-dependent chromatin remodeller Hrp1 in nucleosome disassembly. Our study links topoisomerase activity to the maintenance of open chromatin and regulating transcription in vivo.
DNA 拓扑异构酶调节 DNA 双螺旋的拓扑状态，是 DNA 复制、转录和基因组稳定性过程中的关键酶。我们使用裂殖酵母模型 Schizosaccharomyces pombe 研究 DNA 拓扑异构酶 I 和 II 如何在体内影响染色质动力学和基因表达。我们表明，拓扑异构酶 I 的活性直接需要在基因启动子区域有效解聚核小体。缺乏拓扑异构酶活性会导致核小体占有率增加、组蛋白修饰失调和这些启动子的转录减少。强有力的相关证据表明，拓扑异构酶 I 与 ATP 依赖性染色质重塑酶 Hrp1 合作在核小体解聚中发挥作用。我们的研究将拓扑异构酶活性与维持开放染色质和体内转录调控联系起来。
