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Identification of primary transcriptional regulation of cell cycle-regulated genes upon DNA damage.

机译:DNA损伤后细胞周期调控基因的初级转录调控的鉴定。

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The changes in global gene expression in response to DNA damage may derive from either direct induction or repression by transcriptional regulation or indirectly by synchronization of cells to specific cell cycle phases, such as G1 or G2. We developed a model that successfully estimated the expression levels of >400 cell cycle-regulated genes in normal human fibroblasts based on the proportions of cells in each phase of the cell cycle. By isolating effects on the gene expression associated with the cell cycle phase redistribution after genotoxin treatment, the direct transcriptional target genes were distinguished from genes for which expression changed secondary to cell synchronization. Application of this model to ionizing radiation (IR)-treated normal human fibroblasts identified 150 of 406 cycle-regulated genes as putative direct transcriptional targets of IR-induced DNA damage. Changes in expression of these genes after IR treatment derived from both direct transcriptional regulation and cell cycle synchronization.
机译:响应于DNA损伤的全局基因表达的变化可能源自通过转录调控的直接诱导或抑制,或者是由于细胞与特定细胞周期阶段(例如G1或G2)的同步而间接引起的。我们开发了一个模型,可以根据细胞周期各相中细胞的比例成功估算正常人成纤维细胞中> 400个细胞周期调控基因的表达水平。通过隔离对基因毒素处理后与细胞周期阶段再分布相关的基因表达的影响,可以将直接转录靶基因与那些因细胞同步而发生表达变化的基因区分开。该模型在电离辐射(IR)处理的正常人成纤维细胞中的应用确定了406个周期调控基因中的150个是IR诱导的DNA损伤的假定直接转录靶标。 IR处理后,这些基因的表达变化源自直接转录调控和细胞周期同步。

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