Reference: Pondugula S, et al. (2009) Coupling phosphate homeostasis to cell cycle-specific transcription: mitotic activation of Saccharomyces cerevisiae PHO5 by Mcm1 and Forkhead proteins. Mol Cell Biol 29(18):4891-905

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Abstract

Cells devote considerable resources to nutrient homeostasis, involving nutrient surveillance, acquisition and storage at physiologically relevant concentrations. Many S. cerevisiae transcripts coding for proteins with nutrient uptake functions exhibit peak periodic accumulation during M phase, indicating that an important aspect of nutrient homeostasis involves transcriptional regulation. Inorganic phosphate is a central macronutrient that we previously have shown oscillates inversely with mitotic activation of PHO5. The mechanism of this periodic cell cycle expression remains unknown. To date, only two sequence-specific activators, Pho4 and Pho2, were known to induce PHO5 transcription. Herein, we provide evidence that Mcm1, a MADS-box protein, is essential for PHO5 mitotic activation. In addition, we found that cells simultaneously lacking the forkhead proteins, Fkh1 and Fkh2, exhibited a 2.5-fold decrease in PHO5 expression. The Mcm1-Fkh2 complex, first shown to transactivate genes within the CLB2 cluster that drive G2/M progression, also associated directly at the PHO5 promoter in a cell cycle-dependent manner in chromatin immunoprecipitation assays. Sds3, a component specific to the Rpd3L histone deacetylase complex, was also recruited to PHO5 in G1. These findings provide: i) further mechanistic insight into PHO5 mitotic activation; ii) demonstrate that Mcm1-Fkh2 can function combinatorially with other activators to yield late M/G1 induction and iii) couple the mitotic cell cycle progression machinery to cellular phosphate homeostasis.

Reference Type
Journal Article
Authors
Pondugula S, Neef DW, Voth WP, Darst RP, Dhasarathy A, Reynolds MM, Takahata S, Stillman DJ, Kladde MP
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