Polyphosphate loss promotes SNF/SWI- and Gcn5-dependent mitotic induction of PHO5.
Approximately 800 transcripts in Saccharomyces cerevisiae are cell cycle regulated. The oscillation of approximately 40% of these genes, including a prominent subclass involved in nutrient acquisition, is not understood. To address this problem, we focus on the mitosis-specific activation of the phosphate-responsive promoter, PHO5. We show that the unexpected mitotic induction of the PHO5 acid phosphatase in rich medium requires the transcriptional activators Pho4 and Pho2, the cyclin-dependent kinase inhibitor Pho81, and the chromatin-associated enzymes Gcn5 and Snf2/Swi2. PHO5 mitotic activation is repressed by addition of orthophosphate, which significantly increases cellular polyphosphate. Polyphosphate levels also fluctuate inversely with PHO5 mRNA during the cell cycle, further substantiating an antagonistic link between this phosphate polymer and PHO5 mitotic regulation. Moreover, deletion of PHM3, required for polyphosphate accumulation, leads to premature onset of PHO5 expression, as well as an increased rate, magnitude, and duration of PHO5 activation. Orthophosphate addition, however, represses mitotic PHO5 expression in a phm3delta strain. Thus, polyphosphate per se is not necessary to repress PHO transcription but, when present, replenishes cellular phosphate during nutrient depletion. These results demonstrate a dynamic mechanism of mitotic transcriptional regulation that operates mostly independently of factors that drive progression through the cell cycle.
Neef
Daniel W
DW
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.
Kladde
Michael P
MP
D000251:Adenosine Triphosphatases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D011122:Polyphosphates / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D000251:Adenosine Triphosphatases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D028061:Phosphate Transport Proteins; D011122:Polyphosphates; D011494:Protein Kinases; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C051611:PHO2 protein, S cerevisiae; C081227:PHO81 protein, S cerevisiae; C055831:phosphate permease; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C499333:SNF2 protein, S cerevisiae