“The yeast PHO2 gene also known as BAS2 orGRF10 encodes a homeodomain transcription factor that activates transcription in a combinatorial manner. It appears that Pho2 does not act alone, but with several partner proteins. By itself, Pho2 binds DNA with low affinity 4 and comparison of in vitrobinding sites reveals a relatively nonspecific consensus, ATTA or TAAT 4-6, similar to the consensus for Drosophila homeodomain proteins 2.
Pho2 binds DNA cooperatively with the Pho4 helix-loop-helix factor to activate expression of the PHO5 acid phosphatase 7. Similarly, Pho2 and the Swi5 zinc finger protein bind cooperatively to the HO promoter and contribute to its transcriptional activation 4, 8, 9. Bas1, an myb-like transcription factor, works with Pho2 in the activation of a set of biosynthetic genes, includingHIS4, ADE1, and ADE5,7 5, 10-12.In vitro studies have not shown cooperative DNA binding between Bas1 and Bas2 13, however, these experiments were conducted with in vitro expressed proteins that may not reflect their native state in vivo 14. Additionally, two-hybrid analyses detect an interaction between Pho2 and each of its partners, Pho4, Bas1, and Swi5 9, 15-17, and Pho2 Bas1 interaction has been demonstrated by co-immunoprecipitation 18.”
PHO2 with Bas1–
“Almost twenty genes require the combination of Bas1 and Pho2 for expression, including genes required for metabolism of histidine, purine, and pyrimidine nucleotides and one-carbon units (5, 10-12). The HIS4 gene is activated by one of two pathways, either by Pho2 in combination with Bas1 or by Gcn4 acting alone (5). The ADE5,7 gene is activated by Bas1 and Pho2 but does not require Gcn4 (10,28). TheHIS4 and ADE5,7 genes also differ in their dependence on Pho2 in an assay based on activation by Bas1-VP16 (17);HIS4 expression is strongly dependent on Pho2, whereasADE5,7 exhibits a moderate requirement. Several otherADE genes, typified by ADE1, have only a weak dependence on Pho2 (17).”
“Although SwiS and Ace2 show many parallels, they regulate different genes in vivo (8). Swi5 is an activator of HO, whereas Ace2 cannot activate HO unless ACE2 is overexpressed. Similarly, Ace2 can function as an activator of the chitinase gene CTSJ, but Swi5 cannot. The fact that Swi5 and Ace2 can both bind to the HO and CTSI promoters (unpublished observations) leads to the question of what prevents the cross regulation of CTSI by Swi5 and HO by Ace2.
We believe that the GrflO protein may play a critical role in determining the promoter specificity of Swi5. Grf1O may interact only with SwiS at the HO promoter, thus providing the specificity for Swi5 action at HO. This is supported by experimental observations indicating that Grf1O cannot bind cooperatively with Ace2 to the HO promoter and cannot bind at all to the CTSI promoter (P. R. Dohrmann, R.M.B., and D.J.S., unpublished observations). Another factor may also be present in cells that interacts specifically with Ace2 in binding to the CTS1 promoter, and this protein may provide the specificity for Ace2 regulation of CTSJ. Therefore, the cooperative interaction of the zinc-finger DNA-binding domain protein, SwiS, and the homeodomain DNA-binding protein, Grf1O, may provide the specificity required for the proper transcriptional regulation of the HO gene.”
via Mutations in the Pho2 Bas2 Transcription Factor That Differentially Affect Activation with Its Partner Proteins Bas1, Pho4, and Swi5.
## Another paper pointed out that PHO2 also binds to TRP4 promoter. But the potential role of PHO2 there is less clear — it seems to compete with GCN4 for one of the two UAS sites that the latter binds to. The authors tested several conditions X mutant combinations, and only when the cells were both starved for amino acid and phosphate will there be a reduction in the levels of activation of TRP4 gene expression.