Disease relevance of PHO8

• Upon derepression of PHO8, the chromatin structure changes significantly: The two upstream hypersensitive sites containing the PHO4 binding sites merge, resulting in a long region of hypersensitivity [1].

High impact information on PHO8

• We have previously shown that the disassembly of promoter nucleosomes is obligatory for activation of the yeast PHO5 and PHO8 genes [2].
• Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes [3].
• We show here that on glucose depletion, the S. cerevisiae Isw1 chromatin remodeling complex is required for the displacement of TBP from the PHO8 promoter [4].
• Chromatin remodeling of the yeast PHO8 promoter requires the SAGA histone acetyltransferase complex [5].
• However, in a test of targeting sufficiency, the presence of the entire Kre2p cytoplasmic tail, plus the transmembrane domain and a 36-amino acid residue luminal stem region was required to localize a Pho8p reporter protein to the yeast Golgi [6].

Biological context of PHO8

• The pho9 mutant, whose phenotype is defective in the activity of repressible alkaline phosphatase, produced as much of the PHO8 transcript as did the PHO9+ cells [7].
• Here we show that of two Pho4 binding sites that had been previously mapped at the PHO8 promoter in vitro, only the high affinity one, UASp2, is functional in vivo [8].
• The KRE2 gene is close to PHO8 on chromosome 4, and encodes a predicted 49-kD protein, Kre2p, that probably enters the secretory pathway [9].
• The sequence contains a 1698 bp open reading frame (ORF), and the major PHO8 transcription start point at 32 bp upstream from the ATG codon; several minor transcription start points are located between the major start point and ATG [10].
• The fusion protein also binds to a synthetic oligonucleotide having the same 12-bp nucleotide sequence as the PHO8p DNA from positions -536 to -525 [11].

Anatomical context of PHO8

• In this assay, vacuolar alkaline phosphatase, encoded by PHO8, was targeted to mitochondria in a strain bearing disruption to the genomic PHO8 locus [12].
• The Saccharomyces cerevisiae PHO8 gene product, repressible alkaline phosphatase (ALP), is a glycoprotein enzyme that is localized to the yeast vacuole (lysosome) [13].

Associations of PHO8 with chemical compounds

• Yeast fructose-2,6-bisphosphate 6-phosphatase is encoded by PHO8, the gene for nonspecific repressible alkaline phosphatase [14].

Physical interactions of PHO8

• Specific cis-acting sequence for PHO8 expression interacts with PHO4 protein, a positive regulatory factor, in Saccharomyces cerevisiae [11].

Regulatory relationships of PHO8

• Transcriptional regulation of the yeast PHO8 promoter in comparison to the coregulated PHO5 promoter [8].

Other interactions of PHO8

• By competitive assemblies in the yeast extract system we show that the PHO8 promoter has greater nucleosome positioning power and that the properly positioned nucleosomes are more stable than those at the PHO5 promoter [15].
• We show that nucleosome disassembly also occurs at a second promoter, that of the PHO8 gene, during activation, and we demonstrate that this is also mediated by Asf1p [3].
• The pho4 mutant could not derepress the PHO8 transcript, whereas the pho80 mutant could, irrespective of the amount of Pi in the medium, as has been suggested by genetic study [7].
• Activation of the PHO8 promoter is partially Pho2-dependent [8].
• Depletion of Pbn1p in this strain abrogates processing of the ER precursor forms of PrB, Gas1p, and Pho8p [16].

Analytical, diagnostic and therapeutic context of PHO8

• Gel shift analysis and in vitro footprinting revealed the presence of two PHO4 binding sites at the PHO8 promoter: a low affinity site at -728 and a high affinity site at -532 [1].
• N-terminal sequence analysis of the purified pNPP/FPP phosphatase revealed that it was a truncated form of alkaline phosphatase Pho8 lacking 62 amino acids from the N-terminus and was designated Pho8Delta62 [17].

References