Global control of cell-cycle transcription by coupled CDK and network oscillators

The cell cycle: More regulators to look for During the cell cycle, many genes are transcribed in a periodic manner. A new study in Saccharomyces cerevisiae shows that a significant proportion of these genes continue to cycle in the absence of the major cell cycle regulatory cyclin/CDK complexes that control the G1-S transition. This suggests the existence of additional period regulators responsible for the periodic transcription of genes during the cell cycle. 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.