Tokuda Naoko, Sasai Masaki
Department of Computational Science and Engineering, Nagoya University, Nagoya, Japan.
Department of Computational Science and Engineering, Nagoya University, Nagoya, Japan; Department of Applied Physics, Nagoya University, Nagoya, Japan.
Biophys J. 2017 Feb 7;112(3):491-504. doi: 10.1016/j.bpj.2016.11.3201. Epub 2016 Dec 28.
Recent microscopic and simulation studies have shown that the genome structure fluctuates dynamically in the nuclei of budding yeast Saccharomyces cerevisiae. This genome-wide movement should lead to the fluctuations of individual genes in their territorial regions. This raises an intriguing question of whether the resulting distribution of genes is correlated to their transcriptional activity. An effective method for examining this correlation is to analyze how the spatial distribution of genes and their transcriptional activity are modified by mutation. In this study, we analyzed the modification observed in a budding yeast mutant in which genes necessary for anchoring telomeres to the nuclear envelope, yku70 and esc1, are silenced. Taddei et al. reported that 60 genes are clearly misregulated by this mutation, with 28 and 32 genes downregulated and upregulated, respectively. We calculated the probability density maps of the misregulated genes using a model of dynamical movement of the yeast genome in both wild-type (WT) and yku70 esc1 mutant and showed that the density of downregulated genes is larger near the nucleolus, whereas the density of upregulated genes is larger at the opposite side of the nucleus. By comparing these genes with those highly (top 200 of transcriptome) and lowly (bottom 200) expressed, we showed that the simulated distribution of 28 downregulated (12 out of 32 upregulated) genes has a distinctly larger overlap with the distribution of lowly (highly) expressed genes in the mutant than in the WT. The remaining 20 upregulated genes are localized near the nuclear envelope both in the WT and in the mutant. These results showed that the transcriptional level of genes is affected by their spatial distribution, thus highlighting the importance of the structural regulation in the yeast genome.
最近的微观和模拟研究表明，在出芽酵母酿酒酵母的细胞核中，基因组结构会动态波动。这种全基因组范围的移动应该会导致各个基因在其区域内产生波动。这就引出了一个有趣的问题，即基因的最终分布是否与其转录活性相关。一种检验这种相关性的有效方法是分析基因的空间分布及其转录活性如何因突变而改变。在本研究中，我们分析了在一个出芽酵母突变体中观察到的变化，在该突变体中，将端粒锚定到核膜所需的基因yku70和esc1被沉默。塔代伊等人报告说，有60个基因因这种突变而明显失调，其中28个基因下调，32个基因上调。我们使用酵母基因组在野生型（WT）和yku70 esc1突变体中的动态移动模型，计算了失调基因的概率密度图，结果表明，下调基因的密度在核仁附近更大，而上调基因的密度在细胞核的另一侧更大。通过将这些基因与高表达（转录组前200名）和低表达（后200名）的基因进行比较，我们发现，在突变体中，28个下调基因（32个上调基因中的12个）的模拟分布与低表达（高表达）基因的分布重叠明显大于野生型。其余20个上调基因在野生型和突变体中均位于核膜附近。这些结果表明，基因的转录水平受其空间分布的影响，从而突出了酵母基因组中结构调控的重要性。
