engleski

Transcriptional regulation of the yeast PHO5 gene: a complex interplay of protein-protein and protein-DNA interactions

In the yeast Saccharomyces cerevisiae there are several phosphatases and permeases involved in phosphate uptake and metabolism, and expression of the genes encoding these proteins is coordinately regulated by the phosphate concentration in the medium. The most strongly regulated gene of this PHO system is PHO5, which encodes an isoenzyme of a secreted acid phosphatase. The PHO5 gene is repressed in medium containing phosphate and strongly induced upon phosphate starvation. At least six gene products are directly, or indirectly involved in the regulation of PHO5 transcription. Two transcriptional DNA-binding factors, the basic-helix-loop-helix protein Pho4, a specific activator of the PHO system, and a pleiotropic factor, the homeodomain protein Pho2, coordinately activate the PHO5 promoter. The Pho4 protein is negatively regulated by phosphorylation through a Pho80-Pho85 cyclin-cdk complex. At repressive conditions, phosphorylated Pho4 is localized predominantly in the cytoplasm and that way unable to active PHO5 transcription. However, there is still another, yet unclarified mechanism which regulates PHO5 transcription in response to changes in phosphate concentration. Pho2 serves a dual role in the activation of PHO5. Through cooperative DNA-binding, it increases the binding affinity of Pho4 and at the same time enhances the Pho4 transactivation potential. The Pho5 promoter is repressed by negative regulation of transcriptional activators, and also by a repressive chromatin structure. Four positioned nucleosomes, covering the PHO5 promoter under repressive conditions, are disrupted upon phosphate starvation. The DNA-binding as well as the activation domain of Pho4, are required for the chromatin transition to occur. It seems that the activation domain triggers chromatin disruption through recruitment of proteins capable of alleviating nucleosome repression.

chromatin; PHO5; transcriptional regulation; Saccharomyces cerevisiae

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