Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
Molecular Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
Sci Rep. 2019 Mar 4;9(1):3343. doi: 10.1038/s41598-019-39850-7.
Oscillating gene expression is crucial for correct timing and progression through cell cycle. In Saccharomyces cerevisiae, G1 cyclins Cln1-3 are essential drivers of the cell cycle and have an important role for temporal fine-tuning. We measured time-resolved transcriptome-wide gene expression for wild type and cyclin single and double knockouts over cell cycle with and without osmotic stress. Clustering of expression profiles, peak time detection of oscillating genes, integration with transcription factor network dynamics, and assignment to cell cycle phases allowed us to quantify the effect of genetic or stress perturbations on the duration of cell cycle phases. Cln1 and Cln2 showed functional differences, especially affecting later phases. Deletion of Cln3 led to a delay of START followed by normal progression through later phases. Our data and network analysis suggest mutual effects of cyclins with the transcriptional regulators SBF and MBF.
振荡基因表达对于细胞周期的正确时间和进程至关重要。在酿酒酵母中,G1 周期蛋白 Cln1-3 是细胞周期的重要驱动因素,对时间微调有重要作用。我们在有和没有渗透压胁迫的情况下,测量了野生型和周期蛋白单敲除和双敲除的细胞周期中时分辨转录组范围的基因表达。表达谱聚类、振荡基因峰时检测、转录因子网络动力学整合以及细胞周期阶段分配,使我们能够量化遗传或应激扰动对细胞周期各阶段持续时间的影响。Cln1 和 Cln2 表现出功能差异,特别是对后期阶段有影响。Cln3 的缺失导致 START 的延迟,随后正常进入后期阶段。我们的数据和网络分析表明,细胞周期蛋白与转录调节因子 SBF 和 MBF 之间存在相互作用。