Global control of cell-cycle transcription by coupled CDK and network oscillators
Global control of cell-cycle transcription by coupled CDK and network oscillators
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DOI：
10.1038/nature06955
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发表时间：
2008-06-12
期刊：
影响因子：
64.8
通讯作者：
Haase, Steven B.
中科院分区：
文献类型：
--
作者：
Orlando, David A.;Lin, Charles Y.;Haase, Steven B.
酿酒酵母基因组的显著部分在细胞分裂周期期间周期性地转录（1，2），表明适当定时的基因表达对于调节细胞周期事件是重要的.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（3）。然而，针对少量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（CDK）的活性控制（4）。为了确定细胞周期蛋白- CDK复合物控制整个细胞周期转录程序的程度，我们检测了不表达S期和有丝分裂期细胞周期蛋白的芽殖酵母突变细胞的全基因组转录动力学.在这里，我们表明，一个显着的比例的周期基因异常表达的细胞周期蛋白突变体。尽管缺乏细胞周期蛋白的细胞在G1/S边界被阻断，但近70%的周期基因继续周期性地按计划表达。我们的研究结果表明，虽然CDK具有调节细胞周期转录的功能，但它们并不是唯一负责建立全球周期性转录程序的。我们认为周期性转录是转录因子网络的一种新特性，它可以独立于CDK振荡器，并与CDK振荡器串联。
A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle(1,2), 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(3). However, directed studies interrogating small numbers of genes indicate that their periodic transcription is governed by the activity of cyclin- dependent kinases (CDKs)(4). 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 G1/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.