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Eukaryotic Cell, June 2008, p. 949-957, Vol. 7, No. 6
1535-9778/08/$08.00+0     doi:10.1128/EC.00366-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Transcriptional Repression by the Pho4 Transcription Factor Controls the Timing of SNZ1 Expression ^,

Masafumi Nishizawa,^1* Tae Komai,^2, Nobuyuki Morohashi,³ Mitsuhiro Shimizu,³ and Akio Toh-e^4,

Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582,¹ Department of Material and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681,² Department of Chemistry, Graduate School of Science and Engineering, Meisei University, Tokyo 191-8506,³ Department of Biological Sciences, The University of Tokyo Graduate School of Science, Tokyo 113-0033, Japan⁴

Received 6 October 2007/ Accepted 5 April 2008

Nutrient-sensing kinases play important roles for the yeast Saccharomyces cerevisiae to adapt to new nutrient conditions when the nutrient status changes. Our previous global gene expression analysis revealed that the Pho85 kinase, one of the yeast nutrient-sensing kinases, is involved in the changes in gene expression profiles when yeast cells undergo a diauxic shift. We also found that the stationary phase-specific genes SNZ1 and SNO1, whch share a common promoter, are not properly induced when Pho85 is absent. To examine the role of the kinase in SNZ1/SNO1 regulation, we analyzed their expression during the growth of various yeast mutants, including those affecting Pho85 function or lacking the Pho4 transcription factor, an in vivo substrate of Pho85, and tested Pho4 binding by chromatin immunoprecipitation. Pho4 exhibits temporal binding to the SNZ1/SNO1 promoter to down-regulate the promoter activity, and a pho4 mutation advances the timing of SNZ1/SNO1 expression. SNZ2, another member of the SNZ/SNO family, is expressed at an earlier growth stage than SNZ1, and Pho4 does not affect this timing, although Pho85 is required for SNZ2 expression. Thus, Pho4 appears to regulate the different timing of the expression of the SNZ/SNO family members. Pho4 binding to the SNZ1/SNO1 promoter is accompanied by alterations in chromatin structure, and Rpd3 histone deacetylase is required for the proper timing of SNZ1/SNO1 expression, while Asf1 histone chaperone is indispensable for their expression. These results imply that Pho4 plays positive and negative roles in transcriptional regulation, with both cases involving structural changes in its target chromatin.

Published ahead of print on 11 April 2008.

Supplemental material for this article may be found at http://ec.asm.org/.

Present address: Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.

Present address: Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan.