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Open Access Highly Accessed Research article

Regulation of the yeast metabolic cycle by transcription factors with periodic activities

Aliz R Rao1 and Matteo Pellegrini2

Author Affiliations

1 Bioinformatics Interdepartmental Program, University of California, Los Angeles, USA

2 Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, USA

BMC Systems Biology 2011, 5:160  doi:10.1186/1752-0509-5-160

Published: 12 October 2011



When 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.


Transcription 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.


Analysis 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.