Global effects of DNA replication and DNA replication origin activity on eukaryotic gene expression.

Global effects of DNA replication and DNA replication origin activity on eukaryotic gene expression.
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DOI:
10.1038/msb.2009.70
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发表时间:
2009
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
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这份报告提供了一个全球性的观点,基因表达是如何受到DNA复制的影响。我们分析了同步培养的酿酒酵母的条件下,防止DNA复制启动,而不延迟细胞周期进程。我们使用高阶奇异值分解来整合在多个时间过程中测量的全局mRNA表达,检测和去除实验伪影,并识别跨基因、时间点和条件的表达变异模式的显著组合。我们发现,第一,全球mRNA表达的88%是独立的DNA复制。第二,DNA复制对组蛋白基因有效表达的要求与引发DNA损伤检查点反应的条件无关。第三,来源许可降低了3′端基因的表达,表明下游来源可以调节上游基因的表达。这证实了以前的预测,从数学建模的DNA复制起点的活动和mRNA表达之间的全球因果协调,并表明,数学建模的DNA微阵列数据可以用来正确地预测以前未知的生物模式的调节。
This report provides a global view of how gene expression is affected by DNA replication. We analyzed synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression. We use a higher-order singular value decomposition to integrate the global mRNA expression measured in the multiple time courses, detect and remove experimental artifacts and identify significant combinations of patterns of expression variation across the genes, time points and conditions. We find that, first, ∼88% of the global mRNA expression is independent of DNA replication. Second, the requirement of DNA replication for efficient histone gene expression is independent of conditions that elicit DNA damage checkpoint responses. Third, origin licensing decreases the expression of genes with origins near their 3′ ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation.
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