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Gene Review

GAL1  -  galactokinase

Saccharomyces cerevisiae S288c

Synonyms: Galactokinase, Galactose kinase, YBR020W, YBR0302
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Disease relevance of GAL1

  • One of these regions also showed striking similarity to sequences within the galactokinase protein of Escherichia coli [1].
  • Expression of the LAC9 gene from the yeast Kluyveromyces lactis in HepG2 human hepatoblastoma cells efficiently induced luciferase expression from reporter plasmids containing the four LAC9 binding sites from the K. lactis GAL1-GAL10 gene linked to a basal promoter [2].
  • Interestingly, sites of Pl hypersensitivity localize on the three sequences identified as relevant for the in vitro transcription of the GAL1 moiety of the divergent promoter: the upstream activator sequence (UAS), the TATA sequence, and the RNA initiation site (RIS) [3].
  • We have constructed yeast vectors in which derivatives of the adenovirus E1A gene are expressed from the GAL1 promoter [4].
  • This toxicity was utilized in conjunction with PCR-based mutagenesis of the GAL1 regulatory region to isolate mutant promoters that retained high inducibility but exhibited reduced basal level expression [5].

High impact information on GAL1

  • We also show that PolII is located at both ends of FMP27 when this gene is transcribed from a GAL1 promoter under induced and noninduced conditions [6].
  • Surprisingly, prearresting cells in late mitosis imposes a requirement for SWI/SNF in recruiting Gcn5p HAT activity to the GAL1 promoter, and GAL1 expression also becomes dependent on both chromatin remodeling enzymes [7].
  • H2A.Z is preferentially crosslinked in vivo to intergenic DNA at the PH05 and GAL1 loci, and this association changes with transcriptional activation [8].
  • When the plasmid-borne topoisomerase gene is expressed from an inducible promoter of the GAL1 gene, repression of the gene by dextrose leads to reappearance of the extrachromosomal rDNA rings [9].
  • Examination of the linking number distributions of plasmids bearing the inducible promoters of GAL1 and GAL10 genes indicates that the generation of supercoiled domains of opposite signs is related to transcription [10].

Chemical compound and disease context of GAL1


Biological context of GAL1

  • GAL1-GAL10 divergent promoter region of Saccharomyces cerevisiae contains negative control elements in addition to functionally separate and possibly overlapping upstream activating sequences [15].
  • Previous studies demonstrated that the SAGA (Spt-Ada-Gcn5-Acetyltransferase) complex facilitates the binding of TATA-binding protein (TBP) during transcriptional activation of the GAL1 gene of Saccharomyces cerevisiae [16].
  • By measuring the activity of the single-copy GAL1 promoter in single cells, we found that changes in the activities of either the transcriptional activator, Gal4 (by simple recruitment with synthetic ligands), or the transcriptional repressor, Mig1, generated graded (non-binary) changes in gene expression that were proportional to signal intensity [17].
  • By contrast, activation of the GAL1 gene by galactose addition occurs with normal kinetics [18].
  • Galactokinase encoded by GAL1 is a bifunctional protein required for induction of the GAL genes in Kluyveromyces lactis and is able to suppress the gal3 phenotype in Saccharomyces cerevisiae [19].

Anatomical context of GAL1

  • Metabolic reactivation (incubating spheroplasts with galactose and casamino acids) causes disruption of nucleosomes from the upstream regions of the yeast GAL1, GAL10, and GAL80 genes [20].
  • Stimulation of in vitro processing with energy and cytosol took place efficiently when the expression of PEP4, under control of the GAL1 promoter, was induced then completely repressed before radiolabeling spheroplasts [21].
  • When a sequence that mediates attachment to the nuclear matrix in vitro was inserted into the GAL1 promoter of a lacZ fusion gene, beta-galactosidase synthesis was inhibited [22].
  • When the mutant alpha-tubulins were expressed from the galactose-inducible promoter of GAL1, cells rapidly acquired aberrant microtubule structures [23].
  • Depletion of Rss1p by placing the RSS1 open reading frame (ORF) under control of the GAL1 promoter led to cessation of growth and nuclear accumulation of poly(A)+ RNA without affecting nuclear protein import or nuclear pore complex distribution, suggesting that RSS1 is directly involved in mRNA export [24].

Associations of GAL1 with chemical compounds

  • A single near-consensus synthetic 17 bp oligonucleotide, installed in front of the yeast GAL1 or CYC1 transcription units, conferred a high level of galactose inducibility upon these genes [25].
  • Though the CYC1 promoter is fully induced in yeast grown in glycerol medium, UASC-GAL chimeric promoters containing UASG were repressed as much as 400-fold (UASC-GAL1) or 1350-fold (UASC-GAL10) in this growth medium [15].
  • The data show that the K. lactis GAL1 gene product has, in addition to galactokinase activity, a function required for induction of the lactose system [19].
  • Whereas in the TDH2 promoter permanganate reactivity was entirely abolished, the reactivity at the GAL1 and GAL10 promoter regions was only moderately affected [26].
  • However, the gal1 Delta strain produced much more ethanol, in a complex medium containing glucose, than the GAL1 strain [27].

Physical interactions of GAL1

  • 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) [28].
  • Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a complex of 1:1 stoichiometry [29].

Enzymatic interactions of GAL1


Regulatory relationships of GAL1

  • We show by the following series of experiments that the yeast positive regulatory protein GAL4 binds to four sites in the upstream activating sequence UASG to activate transcription of the adjacent GAL1 and GAL10 genes [25].
  • In complementary experiments, Escherichia coli galactokinase expressed in yeast was shown to complement the gal1 but not the gal3 mutation [30].
  • In vitro, NHP6A stimulated transcription by pol II at the GAL1 promoter three- to fivefold above the level of activation by GAL4-VP16 alone [31].
  • These results imply that multiple copies of MRG19 suppress galactokinase expression probably at the level of transcription [32].
  • To examine the function of Nop4p, we constructed a conditional null allele of NOP4 by placing this gene under the control of the glucose-repressible GAL1 promoter [33].

Other interactions of GAL1

  • Recent work has shown that the yeast histone H4 N-terminus, while not essential for viability, is required for repression of the silent mating loci and activation of GAL1 and PHO5 promoters [34].
  • A 4-base-pair insertion in one of these sites causes constitutive GAL4 synthesis and leads to substantial relief (50-fold) of glucose repression of GAL1 expression [35].
  • Remarkably, the insertion of just two amino acids from Gal1p into the corresponding region of Gal3p confers galactokinase activity onto the resultant protein [36].
  • Unusual aspects of in vitro RNA processing in the 3' regions of the GAL1, GAL7, and GAL10 genes in Saccharomyces cerevisiae [37].
  • Altered in vivo Dam methylase sensitivity is observed at two HPR1-dependent promoters (GAL1 and SUC2) [38].

Analytical, diagnostic and therapeutic context of GAL1


  1. Yeast regulatory gene GAL3: carbon regulation; UASGal elements in common with GAL1, GAL2, GAL7, GAL10, GAL80, and MEL1; encoded protein strikingly similar to yeast and Escherichia coli galactokinases. Bajwa, W., Torchia, T.E., Hopper, J.E. Mol. Cell. Biol. (1988) [Pubmed]
  2. Highly efficient transactivation by the yeast Kluyveromyces lactis transcription factor LAC9 and its inhibition by the negative regulator GAL80 in mammalian cells. Schulz, W.A., Ebling, B., Hasse, A., Zenke, F., Breunig, K. Biol. Chem. Hoppe-Seyler (1993) [Pubmed]
  3. Structure of RNA polymerase II promoters. Conformational alterations and template properties of circularized Saccharomyces cerevisiae GAL1-GAL10 divergent promoters. Camilloni, G., Della Seta, F., Negri, R., Grazia Ficca, A., Di Mauro, E. EMBO J. (1986) [Pubmed]
  4. Cyclic AMP signaling is required for function of the N-terminal and CR1 domains of adenovirus E1A in Saccharomyces cerevisiae. Miller, M.E., Engel, D.A., Smith, M.M. Oncogene (1995) [Pubmed]
  5. Use of a restriction endonuclease cytotoxicity assay to identify inducible GAL1 promoter variants with reduced basal activity. Lewis, L.K., Lobachev, K., Westmoreland, J.W., Karthikeyan, G., Williamson, K.M., Jordan, J.J., Resnick, M.A. Gene (2005) [Pubmed]
  6. Gene loops juxtapose promoters and terminators in yeast. O'Sullivan, J.M., Tan-Wong, S.M., Morillon, A., Lee, B., Coles, J., Mellor, J., Proudfoot, N.J. Nat. Genet. (2004) [Pubmed]
  7. Global role for chromatin remodeling enzymes in mitotic gene expression. Krebs, J.E., Fry, C.J., Samuels, M.L., Peterson, C.L. Cell (2000) [Pubmed]
  8. Histone H2A.Z regulats transcription and is partially redundant with nucleosome remodeling complexes. Santisteban, M.S., Kalashnikova, T., Smith, M.M. Cell (2000) [Pubmed]
  9. A subthreshold level of DNA topoisomerases leads to the excision of yeast rDNA as extrachromosomal rings. Kim, R.A., Wang, J.C. Cell (1989) [Pubmed]
  10. Supercoiling of intracellular DNA can occur in eukaryotic cells. Giaever, G.N., Wang, J.C. Cell (1988) [Pubmed]
  11. Expression and glycosylation of the respiratory syncytial virus G protein in Saccharomyces cerevisiae. Ding, M.X., Wen, D.Z., Schlesinger, M.J., Wertz, G.W., Ball, L.A. Virology (1987) [Pubmed]
  12. Expression of the yeast galactokinase gene in Escherichia coli. Citron, B.A., Feiss, M., Donelson, J.E. Gene (1979) [Pubmed]
  13. Cloning and expression of the yeast galactokinase gene in an Escherichia coli plasmid. Schell, M.A., Wilson, D.B. Gene (1979) [Pubmed]
  14. Quenching accumulation of toxic galactose-1-phosphate as a system to select disruption of protein-protein interactions in vivo. Gunde, T., Tanner, S., Auf der Maur, A., Petrascheck, M., Barberis, A. BioTechniques (2004) [Pubmed]
  15. 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]
  16. The S. cerevisiae SAGA complex functions in vivo as a coactivator for transcriptional activation by Gal4. Larschan, E., Winston, F. Genes Dev. (2001) [Pubmed]
  17. Cell signaling can direct either binary or graded transcriptional responses. Biggar, S.R., Crabtree, G.R. EMBO J. (2001) [Pubmed]
  18. Increasing the rate of chromatin remodeling and gene activation--a novel role for the histone acetyltransferase Gcn5. Barbaric, S., Walker, J., Schmid, A., Svejstrup, J.Q., Hörz, W. EMBO J. (2001) [Pubmed]
  19. Galactokinase encoded by GAL1 is a bifunctional protein required for induction of the GAL genes in Kluyveromyces lactis and is able to suppress the gal3 phenotype in Saccharomyces cerevisiae. Meyer, J., Walker-Jonah, A., Hollenberg, C.P. Mol. Cell. Biol. (1991) [Pubmed]
  20. GAL4/GAL80-dependent nucleosome disruption/deposition on the upstream regions of the yeast GAL1-10 and GAL80 genes. Lohr, D., Lopez, J. J. Biol. Chem. (1995) [Pubmed]
  21. In vitro reconstitution of intercompartmental protein transport to the yeast vacuole. Vida, T.A., Graham, T.R., Emr, S.D. J. Cell Biol. (1990) [Pubmed]
  22. Yeast calmodulin and a conserved nuclear protein participate in the in vivo binding of a matrix association region. Fishel, B.R., Sperry, A.O., Garrard, W.T. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  23. Dominant-lethal alpha-tubulin mutants defective in microtubule depolymerization in yeast. Anders, K.R., Botstein, D. Mol. Biol. Cell (2001) [Pubmed]
  24. The product of the Saccharomyces cerevisiae RSS1 gene, identified as a high-copy suppressor of the rat7-1 temperature-sensitive allele of the RAT7/NUP159 nucleoporin, is required for efficient mRNA export. Del Priore, V., Snay, C.A., Bahr, A., Cole, C.N. Mol. Biol. Cell (1996) [Pubmed]
  25. Specific DNA binding of GAL4, a positive regulatory protein of yeast. Giniger, E., Varnum, S.M., Ptashne, M. Cell (1985) [Pubmed]
  26. Rad25p, a DNA helicase subunit of yeast transcription factor TFIIH, is required for promoter escape in vivo. Ostapenko, D., Gileadi, O. Gene (2000) [Pubmed]
  27. Characteristics of Saccharomyces cerevisiae gal1 Delta and gal1 Delta hxk2 Delta mutants expressing recombinant proteins from the GAL promoter. Kang, H.A., Kang, W.K., Go, S.M., Rezaee, A., Krishna, S.H., Rhee, S.K., Kim, J.Y. Biotechnol. Bioeng. (2005) [Pubmed]
  28. In vivo DNA-binding properties of a yeast transcription activator protein. Selleck, S.B., Majors, J.E. Mol. Cell. Biol. (1987) [Pubmed]
  29. Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a complex of 1:1 stoichiometry. Timson, D.J., Ross, H.C., Reece, R.J. Biochem. J. (2002) [Pubmed]
  30. 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]
  31. Yeast HMG proteins NHP6A/B potentiate promoter-specific transcriptional activation in vivo and assembly of preinitiation complexes in vitro. Paull, T.T., Carey, M., Johnson, R.C. Genes Dev. (1996) [Pubmed]
  32. Multiple copies of MRG19 suppress transcription of the GAL1 promoter in a GAL80-dependent manner in Saccharomyces cerevisiae. Kabir, M.A., Khanday, F.A., Mehta, D.V., Bhat, P.J. Mol. Gen. Genet. (2000) [Pubmed]
  33. The yeast NOP4 gene product is an essential nucleolar protein required for pre-rRNA processing and accumulation of 60S ribosomal subunits. Sun, C., Woolford, J.L. EMBO J. (1994) [Pubmed]
  34. Histone H3 N-terminal mutations allow hyperactivation of the yeast GAL1 gene in vivo. Mann, R.K., Grunstein, M. EMBO J. (1992) [Pubmed]
  35. 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]
  36. The insertion of two amino acids into a transcriptional inducer converts it into a galactokinase. Platt, A., Ross, H.C., Hankin, S., Reece, R.J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  37. Unusual aspects of in vitro RNA processing in the 3' regions of the GAL1, GAL7, and GAL10 genes in Saccharomyces cerevisiae. Sadhale, P.P., Platt, T. Mol. Cell. Biol. (1992) [Pubmed]
  38. HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae. Zhu, Y., Peterson, C.L., Christman, M.F. Mol. Cell. Biol. (1995) [Pubmed]
  39. The Regulatory Roles of the Galactose Permease and Kinase in the Induction Response of the GAL Network in Saccharomyces cerevisiae. Hawkins, K.M., Smolke, C.D. J. Biol. Chem. (2006) [Pubmed]
  40. Unique distribution of GAL genes on chromosome XI in the yeast Saccharomyces naganishii. Kodama, T., Hisatomi, T., Kakiuchi, M., Aya, R., Yoshida, K., Bando, Y., Takami, T., Tsuboi, M. Curr. Microbiol. (2003) [Pubmed]
  41. Galactose induction in yeast involves association of Gal80p with Gal1p or Gal3p. Vollenbroich, V., Meyer, J., Engels, R., Cardinali, G., Menezes, R.A., Hollenberg, C.P. Mol. Gen. Genet. (1999) [Pubmed]
  42. The Saccharomyces cerevisiae Srb8-Srb11 complex functions with the SAGA complex during Gal4-activated transcription. Larschan, E., Winston, F. Mol. Cell. Biol. (2005) [Pubmed]
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