Regulation of the Yeast PHO5 and PHO8 Genes: A Network of Regulatory Proteins, Transcription Factors and Chromatin
Slobodan Barbarić1*, Philip D. Gregory2, Martin Münsterkötter2, Tamara Korica1 and Wolfram Hörz2
1 Laboratory of Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia
2 Institut für Physiologische Chemie, Universität München, Schillerstr. 44, D-80336 Munich, Germany
Article history:
Received January 25, 1999
Accepted February 15, 1999
Key words:
transcriptional regulation, chromatin, PHO5, PHO8, Saccharomyces cerevisiae
Summary:
The yeast Saccharomyces cerevisiae contains several phosphatases and permeases involved in phosphate uptake and metabolism, the synthesis of which is regulated in response to the phosphate concentration in the growth medium. In phosphate containing media, transcription of these genes is repressed, while phosphate starvation results in strong induction. The most strongly regulated gene of this PHO system is PHO5 which encodes a secreted non-specific acid phosphatase. Repression of PHO5 transcription is achieved through negative regulation of the specific activator, Pho4. Under repressing conditions Pho4 is phosphorylated by the Pho80–Pho85 cyclin-cdk complex, and transcription prevented by its subsequent export out of the nucleus by interaction with the Msn5 receptor. Under phosphate limitation, the Pho80–Pho85 complex is inhibited through the action of the cyclin inhibitor Pho81, which results in the accumulation of non-phosphorylated Pho4 in the nucleus. However, in addition to the regulation of the Pho4 subcellular localization, there is another as yet unclarified mechanism which regulates PHO5 transcription. Activation of PHO5 transcription requires the cooperative interaction of Pho4 with the pleiotropic homeodomain protein Pho2. Pho2 plays a role in increasing both the DNA binding affinity and transactivation potential of Pho4. The PHO5 promoter is also regulated through a repressive chromatin structure. Upon induction, massive, Pho4-dependent remodeling of chromatin occurs, which is a prerequisite for promoter activation. The PHO8 gene, encoding a non-specific alkaline phosphatase, is coordinately regulated with PHO5 through the same set of regulatory proteins and also through chromatin repression. However, in comparison to PHO5, the PHO8 promoter is transcriptionally rather weak. This low level of PHO8 induction can be explained by the inability of Pho4 to accomplish full chromatin remodeling at this promoter. Complexes which influence the ability to remodel chromatin are discussed. These results highlight the importance of chromatin structure in the regulation of promoter activity.
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