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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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摘要

A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle, , suggesting that properly timed gene expression is important for regulating cell cycle events. Genomic analyses of transcription factor localization and expression dynamics suggest that a network of sequentially expressed transcription factors could control the temporal program 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 program 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 were aberrantly expressed in the cyclin mutant. Surprisingly, although cells lacking cyclins are blocked at the G1/S border, nearly 70% of periodic genes continued to be expressed periodically and on schedule. Our findings reveal that while CDKs play a role in the regulation of cell cycle transcription, they are not solely responsible for establishing the global periodic transcription program. We propose that periodic transcription is an emergent property of a transcription factor network that can function as a cell cycle oscillator independent 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。为了确定细胞周期蛋白/ CDK复合物控制全球细胞周期转录程序的程度,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。出人意料的是,尽管缺乏细胞周期蛋白的细胞在G1 / S边界被阻滞,但近70%的周期基因仍继续按计划定期表达。我们的发现表明,尽管CDK在细胞周期转录的调控中发挥作用,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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