Reconciling conflicting models for global control of cell-cycle transcription

Models for the control of global cell-cycle transcription have advanced from a CDK-APC/C oscillator, a transcription factor (TF) network, to coupled CDK-APC/C and TF networks. Nonetheless, current models were challenged by a recent study that concluded that the cell-cycle transcriptional program is primarily controlled by a CDK-APC/C oscillator in budding yeast. Here we report an analysis of the transcriptome dynamics in cyclin mutant cells that were not queried in the previous study. We find that B-cyclin oscillation is not essential for control of phase-specific transcription. Using a mathematical model, we demonstrate that the function of network TFs can be retained in the face of significant reductions in transcript levels. Finally, we show that cells arrested at mitotic exit with non-oscillating levels of B-cyclins continue to cycle transcriptionally. Taken together, these findings support a critical role of a TF network and a requirement for CDK activities that need not be periodic.

调控全局细胞周期转录的模型，已从细胞周期蛋白依赖性激酶-后期促进复合物（CDK-APC/C）振荡器、转录因子（TF）网络，演进至耦合的CDK-APC/C与TF网络。然而，近期一项研究提出出芽酵母的细胞周期转录程序主要由CDK-APC/C振荡器调控，这对现有模型构成了挑战。本研究对此前研究未涉及的周期蛋白突变体细胞的转录组动态展开分析。我们发现，B型周期蛋白（B-cyclin）的振荡对于时期特异性转录的调控并非必需。通过构建数学模型，我们证实即便转录本水平大幅降低，网络内转录因子的功能仍可得以维持。最后，我们证实，当细胞因B型周期蛋白水平不再振荡而阻滞于有丝分裂退出阶段时，其转录过程仍可周期性运行。综上，本研究结果支持转录因子网络发挥关键调控作用，同时表明 CDK 活性无需呈周期性变化。