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Global control of cell-cycle transcription by coupled CDK and network oscillators

机译:CDK和网络振荡器耦合对细胞周期转录的全局控制

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A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle, indicating that properly timed gene expression is important for regulating cell-cycle events. Genomic analyses of the localization and expression dynamics of transcription factors suggest that a network of sequentially expressed transcription factors could control the temporal programme of transcription during the cell cycle. However, directed studies interrogating small numbers of genes indicate that their periodic transcription is governed by the activity of cyclin-dependent kinases (CDKs). To determine the extent to which the global cell-cycle transcription programme is controlled by cyclin-CDK complexes, we examined genome-wide transcription dynamics in budding yeast mutant cells that do not express S-phase and mitotic cyclins. Here we show that a significant fraction of periodic genes are aberrantly expressed in the cyclin mutant. Although cells lacking cyclins are blocked at the Gl/S border, nearly 70% of periodic genes continued to be expressed periodically and on schedule. Our findings reveal that although CDKs have a function in the regulation of cell-cycle transcription, they are not solely responsible for establishing the global periodic transcription programme. We propose that periodic transcription is an emergent property of a transcription factor network that can function as a cell-cycle oscillator independently of, and in tandem with, the CDK oscillator.
机译:啤酒酵母基因组的很大一部分是在细胞分裂周期中周期性转录的,这表明正确定时的基因表达对于调节细胞周期事件很重要。转录因子的定位和表达动力学的基因组分析表明,顺序表达的转录因子网络可以控制细胞周期中转录的时间程序。但是,针对少数基因的定向研究表明,它们的周期性转录受细胞周期蛋白依赖性激酶(CDKs)的活性支配。为了确定全球细胞周期转录程序受细胞周期蛋白CDK复合体控制的程度,我们检查了不表达S期和有丝分裂细胞周期蛋白的出芽酵母突变细胞中全基因组转录动态。在这里,我们显示周期蛋白的很大一部分在细胞周期蛋白突变体中异常表达。尽管缺乏细胞周期蛋白的细胞在G1 / S边界被阻断,但是将近70%的周期性基因继续按计划周期性地表达。我们的发现表明,尽管CDK在调节细胞周期转录中具有功能,但它们并不完全负责建立全局周期性转录程序。我们建议定期转录是转录因子网络的新兴属性,可以独立于CDK振荡器并与CDK振荡器一起用作细胞周期振荡器。

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