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细胞周期调控转录:有效运用基因组学工具包

Cell cycle-regulated transcription: effectively using a genomics toolbox.

作者信息

Bristow Sara L, Leman Adam R, Haase Steven B

机构信息

Department of Biology, Duke University, 90338, Science Drive, Durham, NC, 27708, USA.

出版信息

Methods Mol Biol. 2014;1170:3-27. doi: 10.1007/978-1-4939-0888-2_1.

Abstract

The cell cycle comprises a series of temporally ordered events that occur sequentially, including DNA replication, centrosome duplication, mitosis, and cytokinesis. What are the regulatory mechanisms that ensure proper timing and coordination of events during the cell cycle? Biochemical and genetic screens have identified a number of cell-cycle regulators, and it was recognized early on that many of the genes encoding cell-cycle regulators, including cyclins, were transcribed only in distinct phases of the cell cycle. Thus, "just in time" expression is likely an important part of the mechanism that maintains the proper temporal order of cell cycle events. New high-throughput technologies for measuring transcript levels have revealed that a large percentage of the Saccharomyces cerevisiae transcriptome (~20 %) is cell cycle regulated. Similarly, a substantial fraction of the mammalian transcriptome is cell cycle-regulated. Over the past 25 years, many studies have been undertaken to determine how gene expression is regulated during the cell cycle. In this review, we discuss contemporary models for the control of cell cycle-regulated transcription, and how this transcription program is coordinated with other cell cycle events in S. cerevisiae. In addition, we address the genomic approaches and analytical methods that enabled contemporary models of cell cycle transcription. Finally, we address current and future technologies that will aid in further understanding the role of periodic transcription during cell cycle progression.

摘要

细胞周期由一系列按时间顺序依次发生的事件组成,包括DNA复制、中心体复制、有丝分裂和胞质分裂。确保细胞周期中各事件的时间安排和协调的调控机制是什么?生化和遗传学筛选已经鉴定出许多细胞周期调节因子,并且很早就认识到许多编码细胞周期调节因子的基因,包括细胞周期蛋白,仅在细胞周期的不同阶段转录。因此,“适时”表达可能是维持细胞周期事件正确时间顺序的机制的重要组成部分。用于测量转录水平的新高通量技术表明,酿酒酵母转录组的很大一部分(约20%)受细胞周期调控。同样,哺乳动物转录组的很大一部分也受细胞周期调控。在过去25年中,人们进行了许多研究来确定细胞周期中基因表达是如何调控的。在这篇综述中,我们讨论了控制细胞周期调控转录的当代模型,以及这个转录程序是如何与酿酒酵母中的其他细胞周期事件协调的。此外,我们介绍了促成细胞周期转录当代模型的基因组方法和分析方法。最后,我们介绍了有助于进一步理解细胞周期进程中周期性转录作用的当前和未来技术。

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