Abstract
BackgroundWhen growing budding yeast under continuous, nutrient-limited conditions, over half of yeast genes exhibit periodic expression patterns. Periodicity can also be observed in respiration, in the timing of cell division, as well as in various metabolite levels. Knowing the transcription factors involved in the yeast metabolic cycle is helpful for determining the cascade of regulatory events that cause these patterns.ResultsTranscription factor activities were estimated by linear regression using time series and genome-wide transcription factor binding data. Time-translation matrices were estimated using least squares and were used to model the interactions between the most significant transcription factors. The top transcription factors have functions involving respiration, cell cycle events, amino acid metabolism and glycolysis. Key regulators of transitions between phases of the yeast metabolic cycle appear to be Hap1, Hap4, Gcn4, Msn4, Swi6 and Adr1.ConclusionsAnalysis of the phases at which transcription factor activities peak supports previous findings suggesting that the various cellular functions occur during specific phases of the yeast metabolic cycle.
Highlights
When growing budding yeast under continuous, nutrient-limited conditions, over half of yeast genes exhibit periodic expression patterns
About half of the transcription factors are known cell cycle regulators. This is not surprising, since roughly 50% of yeast cells in the culture divide in each cycle, and cell division is always initiated within a short window during the yeast metabolic cycle, in the R/B phase [2]
Many of the transcription factors are known to be associated with pathways that may be related to phases or transitions in the yeast metabolic cycle, such as the diauxic shift, response to oxidative stress, or cell cycle initiation
Summary
When growing budding yeast under continuous, nutrient-limited conditions, over half of yeast genes exhibit periodic expression patterns. Periodicity can be observed in respiration, in the timing of cell division, as well as in various metabolite levels. Budding yeast cells (Saccharomyces cerevisiae) exhibit oscillatory dynamics in several cellular pathways, such as those involving the cell cycle, glucose metabolism, and respiration. Previous studies [1,2] have observed metabolic cycles in yeast cultures in which most genes were expressed in a cyclic manner. These cycles are self-sustaining oscillatory patterns: once cells are synchronized, they continue to exhibit robust oscillations indefinitely [3,4]. There is debate about the relationship between the cell division cycle and the yeast respiratory oscillations, and whether the short- and long-phase oscillations are fundamentally
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