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Gene Review

GAL4  -  Gal4p

Saccharomyces cerevisiae S288c

Synonyms: Regulatory protein GAL4, YPL248C
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Disease relevance of GAL4


High impact information on GAL4

  • Destruction of transcriptionally active Gal4 depends on an F box protein called Dsg1/Mdm30 [6].
  • Analysis of the phenotype of dsg1-null yeast reveals a striking disconnect between GAL gene RNA and protein levels; in the absence of Dsg1, Gal4 target genes are transcribed, but the resulting RNAs are not translated [6].
  • The yeast transcriptional activator Gal4 has served as a paradigm for understanding how eukaryotic cells mount rapid transcriptional responses to environmental changes [7].
  • We report that a Spo11 construct bearing the Gal4 DNA binding domain not only rescues spo11Delta spore inviability and catalyzes DSB formation at natural sites but also strongly stimulates DSB formation near Gal4 binding sites [8].
  • By fusing all or part of SOX9 to the DNA-binding domain of yeast GAL4, the transactivating function was mapped to a transcription activation (TA) domain at the C terminus of SOX9 [9].

Chemical compound and disease context of GAL4


Biological context of GAL4

  • Mutations in SUG1 were isolated as suppressors of a mutation in the transcriptional activation domain of GAL4 [15].
  • The SWI/SNF complex caused a 10- to 30-fold stimulation in the binding of GAL4 derivatives to nucleosomal DNA in a reaction that required adenosine triphosphate (ATP) hydrolysis but was activation domain-independent [16].
  • Thus, GAL4, which encodes an activator of the GAL genes, is repressed by MIG1, a zinc finger protein that binds to the GAL4 promoter [17].
  • We also measure stimulation of transcription by pairs of GAL4 binding sites and find that the activities of low-affinity binding sites combine synergistically, whereas the activities of high-affinity binding sites combine only additively [18].
  • GAL4 promoter sequences that mediate glucose repression were found to lie downstream of positively acting elements that may be "TATA boxes." Two nearly identical sequences (10/12 base pairs) in this region that may be binding sites for the MIG1 protein were identified as functional glucose-control elements [19].

Anatomical context of GAL4


Associations of GAL4 with chemical compounds

  • Further experiments suggest that one mechanism of glucose repression is inhibition of the binding of GAL4 protein to DNA [1].
  • In the yeast Saccharomyces cerevisiae regulation of the galactose/melibiose regulon rests on a dosage-dependent functional interplay between the positive regulator of transcription, the GAL4 protein, and the negative regulator, GAL80 protein [25].
  • One type of these constructions produces a GAL4 protein that lacks its normal NH2 terminus [25].
  • We have identified the promoter region of the GAL10 gene (whose product is UDP-galactose epimerase) of Saccharomyces cerevisiae; this promoter mediates galactose induction of transcription in conjunction with the product of the GAL4 regulatory gene [26].
  • We further show that lysine 36 of histone H3 at GAL4 is methylated and that this methylation is dependent upon the presence of SET2 [27].

Physical interactions of GAL4

  • Stimulation of GAL4 binding by the complex was abolished by a mutant SWI2 subunit, and was increased by the presence of a histone-binding protein, nucleoplasmin [16].
  • Here, we show that a small carboxy-terminal domain of RAP1 is sufficient to establish repression when fused to the GAL4 DNA-binding domain (GBD) and targeted to mutated HMR silencers containing GAL4 DNA-binding sites [28].
  • Deletion analysis of the his3-G25 promoter showed a correlation between the number of GAL4p binding sites and the relative level of NGG1p activity [29].
  • We have used the photofootprinting technique to determine during which of three regulated states (uninduced, induced, and catabolite repressed) the transcriptional activator protein encoded by GAL4 binds to its recognition sites within the GAL1-GAL10 upstream activating sequence (UASG) [30].
  • Mini-GAL4 derivatives having weakened interactions with TATA-binding protein and TFIIB exhibit a strong dependence on GCN5 for both transcriptional activation and TALS remodeling not seen for native GAL4 [31].

Regulatory relationships of GAL4

  • These results, combined with those of earlier studies, suggest the possibility that GAL4 normally induces transcription of GAL1 and GAL10 by blocking the activity of these negative control elements, in addition to stimulating transcription by a mechanism of positive control [32].
  • These results suggest that NGG1p acts to inhibit GAL4p function in glucose medium [29].
  • Analysis of the GAL3 signal transduction pathway activating GAL4 protein-dependent transcription in Saccharomyces cerevisiae [33].
  • Expression of the gene GCY1 in Saccharomyces cerevisiae is induced by about 25-fold in the presence of galactose as a result of activation by Gal4p [34].
  • These results are the first indication that the subcellular distribution dynamics of the Gal3 and Gal80 proteins play a role in regulating Gal4p-mediated GAL gene expression in vivo [35].

Other interactions of GAL4

  • GAL11P: a yeast mutation that potentiates the effect of weak GAL4-derived activators [36].
  • Strikingly, the mutant extract responded like wild type to GAL4-HAP4 [2].
  • Several yeast upstream transcriptional activators, such as GCN4, GAL4 and HAP1, seem to contain separate domains for binding to DNA and activating transcription [37].
  • Replacement of this region with the activation domain of GAL4 restored activity, suggesting that it provides the principal activation domain to the bound HAP2/3/4 complex [38].
  • This cdc39-2 mutation causes increased basal transcription of many, but not all genes, as well as increased transcriptional activation by GCN4 and GAL4 [39].

Analytical, diagnostic and therapeutic context of GAL4


  1. Specific DNA binding of GAL4, a positive regulatory protein of yeast. Giniger, E., Varnum, S.M., Ptashne, M. Cell (1985) [Pubmed]
  2. Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Berger, S.L., Piña, B., Silverman, N., Marcus, G.A., Agapite, J., Regier, J.L., Triezenberg, S.J., Guarente, L. Cell (1992) [Pubmed]
  3. Mechanism of action of a yeast activator: direct effect of GAL4 derivatives on mammalian TFIID-promoter interactions. Horikoshi, M., Carey, M.F., Kakidani, H., Roeder, R.G. Cell (1988) [Pubmed]
  4. GAL4 activates gene expression in mammalian cells. Kakidani, H., Ptashne, M. Cell (1988) [Pubmed]
  5. Alterations in a yeast protein resembling HIV Tat-binding protein relieve requirement for an acidic activation domain in GAL4. Swaffield, J.C., Bromberg, J.F., Johnston, S.A. Nature (1992) [Pubmed]
  6. The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing. Muratani, M., Kung, C., Shokat, K.M., Tansey, W.P. Cell (2005) [Pubmed]
  7. An unexpected role for ubiquitylation of a transcriptional activator. Arndt, K., Winston, F. Cell (2005) [Pubmed]
  8. Targeted stimulation of meiotic recombination. Peciña, A., Smith, K.N., Mézard, C., Murakami, H., Ohta, K., Nicolas, A. Cell (2002) [Pubmed]
  9. Sex reversal by loss of the C-terminal transactivation domain of human SOX9. Südbeck, P., Schmitz, M.L., Baeuerle, P.A., Scherer, G. Nat. Genet. (1996) [Pubmed]
  10. Regulation of human immunodeficiency virus enhancer function by PRDII-BF1 and c-rel gene products. Muchardt, C., Seeler, J.S., Nirula, A., Shurland, D.L., Gaynor, R.B. J. Virol. (1992) [Pubmed]
  11. Autonomous parvovirus transduction of a gene under control of tissue-specific or inducible promoters. Maxwell, I.H., Spitzer, A.L., Long, C.J., Maxwell, F. Gene Ther. (1996) [Pubmed]
  12. A chimeric fusion protein containing transforming growth factor-alpha mediates gene transfer via binding to the EGF receptor. Fominaya, J., Uherek, C., Wels, W. Gene Ther. (1998) [Pubmed]
  13. Overproduction and single-step purification of GAL4 fusion proteins from Escherichia coli. Reece, R.J., Rickles, R.J., Ptashne, M. Gene (1993) [Pubmed]
  14. Alteration of specific amino acid residues in the acidic domain I of VSV phosphoprotein (P) converts a GAL4-P(I) hybrid into a transcriptional activator. Takacs, A.M., Perrine, K.G., Barik, S., Banerjee, A.K. New Biol. (1991) [Pubmed]
  15. Identification of the gal4 suppressor Sug1 as a subunit of the yeast 26S proteasome. Rubin, D.M., Coux, O., Wefes, I., Hengartner, C., Young, R.A., Goldberg, A.L., Finley, D. Nature (1996) [Pubmed]
  16. Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Côté, J., Quinn, J., Workman, J.L., Peterson, C.L. Science (1994) [Pubmed]
  17. Control of yeast GAL genes by MIG1 repressor: a transcriptional cascade in the glucose response. Nehlin, J.O., Carlberg, M., Ronne, H. EMBO J. (1991) [Pubmed]
  18. Cooperative DNA binding of the yeast transcriptional activator GAL4. Giniger, E., Ptashne, M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  19. Regulated expression of the GAL4 activator gene in yeast provides a sensitive genetic switch for glucose repression. Griggs, D.W., Johnston, M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  20. The yeast UASG is a transcriptional enhancer in human HeLa cells in the presence of the GAL4 trans-activator. Webster, N., Jin, J.R., Green, S., Hollis, M., Chambon, P. Cell (1988) [Pubmed]
  21. Amino terminus of the yeast GAL4 gene product is sufficient for nuclear localization. Silver, P.A., Keegan, L.P., Ptashine, M. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  22. Glutamine-rich domains activate transcription in yeast Saccharomyces cerevisiae. Xiao, H., Jeang, K.T. J. Biol. Chem. (1998) [Pubmed]
  23. Phosphorylation of Ga14p at a single C-terminal residue is necessary for galactose-inducible transcription. Sadowski, I., Costa, C., Dhanawansa, R. Mol. Cell. Biol. (1996) [Pubmed]
  24. Perinuclear localization of chromatin facilitates transcriptional silencing. Andrulis, E.D., Neiman, A.M., Zappulla, D.C., Sternglanz, R. Nature (1998) [Pubmed]
  25. Functional domains of the yeast regulatory protein GAL4. Johnston, S.A., Zavortink, M.J., Debouck, C., Hopper, J.E. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  26. A GAL10-CYC1 hybrid yeast promoter identifies the GAL4 regulatory region as an upstream site. Guarente, L., Yocum, R.R., Gifford, P. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  27. Set2-catalyzed methylation of histone H3 represses basal expression of GAL4 in Saccharomyces cerevisiae. Landry, J., Sutton, A., Hesman, T., Min, J., Xu, R.M., Johnston, M., Sternglanz, R. Mol. Cell. Biol. (2003) [Pubmed]
  28. Action of a RAP1 carboxy-terminal silencing domain reveals an underlying competition between HMR and telomeres in yeast. Buck, S.W., Shore, D. Genes Dev. (1995) [Pubmed]
  29. Characterization of NGG1, a novel yeast gene required for glucose repression of GAL4p-regulated transcription. Brandl, C.J., Furlanetto, A.M., Martens, J.A., Hamilton, K.S. EMBO J. (1993) [Pubmed]
  30. In vivo DNA-binding properties of a yeast transcription activator protein. Selleck, S.B., Majors, J.E. Mol. Cell. Biol. (1987) [Pubmed]
  31. GCN5 dependence of chromatin remodeling and transcriptional activation by the GAL4 and VP16 activation domains in budding yeast. Stafford, G.A., Morse, R.H. Mol. Cell. Biol. (2001) [Pubmed]
  32. GAL1-GAL10 divergent promoter region of Saccharomyces cerevisiae contains negative control elements in addition to functionally separate and possibly overlapping upstream activating sequences. West, R.W., Chen, S.M., Putz, H., Butler, G., Banerjee, M. Genes Dev. (1987) [Pubmed]
  33. Analysis of the GAL3 signal transduction pathway activating GAL4 protein-dependent transcription in Saccharomyces cerevisiae. Bhat, P.J., Oh, D., Hopper, J.E. Genetics (1990) [Pubmed]
  34. The general regulatory factor Reb1p controls basal, but not Gal4p-mediated, transcription of the GCY1 gene in yeast. Angermayr, M., Bandlow, W. Mol. Gen. Genet. (1997) [Pubmed]
  35. Evidence for Gal3p's cytoplasmic location and Gal80p's dual cytoplasmic-nuclear location implicates new mechanisms for controlling Gal4p activity in Saccharomyces cerevisiae. Peng, G., Hopper, J.E. Mol. Cell. Biol. (2000) [Pubmed]
  36. GAL11P: a yeast mutation that potentiates the effect of weak GAL4-derived activators. Himmelfarb, H.J., Pearlberg, J., Last, D.H., Ptashne, M. Cell (1990) [Pubmed]
  37. Mutations that alter transcriptional activation but not DNA binding in the zinc finger of yeast activator HAPI. Kim, K.S., Guarente, L. Nature (1989) [Pubmed]
  38. Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer. Forsburg, S.L., Guarente, L. Genes Dev. (1989) [Pubmed]
  39. CDC39, an essential nuclear protein that negatively regulates transcription and differentially affects the constitutive and inducible HIS3 promoters. Collart, M.A., Struhl, K. EMBO J. (1993) [Pubmed]
  40. Purification and characterization of the yeast transcriptional activator GAL4. Parthun, M.R., Jaehning, J.A. J. Biol. Chem. (1990) [Pubmed]
  41. The EGD1 product, a yeast homolog of human BTF3, may be involved in GAL4 DNA binding. Parthun, M.R., Mangus, D.A., Jaehning, J.A. Mol. Cell. Biol. (1992) [Pubmed]
  42. Regulated phosphorylation and dephosphorylation of GAL4, a transcriptional activator. Mylin, L.M., Bhat, J.P., Hopper, J.E. Genes Dev. (1989) [Pubmed]
  43. An activator target in the RNA polymerase II holoenzyme. Koh, S.S., Ansari, A.Z., Ptashne, M., Young, R.A. Mol. Cell (1998) [Pubmed]
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