The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

HIS3  -  imidazoleglycerol-phosphate dehydratase HIS3

Saccharomyces cerevisiae S288c

Synonyms: HIS10, HIS8, IGPD, Imidazoleglycerol-phosphate dehydratase, YOR202W
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of HIS3

  • We now report that nucleosome loss activates the expression of two additional promoters that are normally induced by independent mechanisms: CUP1 (induced by heavy-metal toxicity) and HIS3 (induced by amino acid starvation) [1].
  • Yeast HIS3 expression in Escherichia coli depends upon fortuitous homology between eukaryotic and prokaryotic promoter elements [2].
  • By using derivatives in which his3 sequences are replaced by a small fragment of coliphage M13 DNA, three properties of the his3 promoter were established [3].
  • HinfI hypersensitivity within the his3 promoter region is locally determined, since it was observed when this region was translocated to the middle of the ade2 structural gene [4].
  • Imidazole glycerol phosphate dehydratase (IGPD) catalyses the dehydration of imidazole glycerol phosphate to imidazole acetol phosphate, an important late step in the biosynthesis of histidine [5].

High impact information on HIS3

  • Transcriptional activation of HIS3 and HIS4 by Gcn4 is triggered by UV irradiation in a Ras-dependent fashion [6].
  • We used a HIS3 reporter gene to show that RNA-mediated recombination occurs in yeast [7].
  • Two RNA-mediated recombination events were detected: homologous recombination between the cDNA and plasmid his3 sequences, resulting in intron loss, and insertion of the cDNA into the chromosome in the absence of HIS3 homology [7].
  • The chromosomal His3+ prototrophs showed many hallmarks of naturally occurring pseudogenes [7].
  • Specifically, a DNA segment containing this regulatory site was fused upstream of the intact his3 promoter region and structural gene at several locations [8].

Biological context of HIS3


Anatomical context of HIS3

  • In the present study we show that when a 1.77 kb BamHI DNA fragment harbouring the his3 gene of Saccharomyces cerevisiae was microinjected into the macronucleus, a fraction of the molecules are integrated into the chromosome via an illegitimate recombination process [14].

Associations of HIS3 with chemical compounds

  • In Saccharomyces cerevisiae, 3-amino-1,2,4-triazole (aminotriazole) competitively inhibits the activity of imidazoleglycerolphosphate dehydratase, the product of the HIS3 gene [15].
  • From this library, LEU2 and HIS3 cDNAs were recovered at a frequency of about 1 in 10(4) and in 12 out of 13 cases these were expressed in a galactose-dependent manner [16].
  • In contrast, only the downstream leu2 fragment was transcribed upon leucine repression, and the HIS3 insert in the leu2 region remained intact [17].
  • Upon introduction of parasite CpMBF1 into S. cerevisiae, 3-amino triazole resistance of the MBF1-deficient strain was restored to wild-type levels, and Northern blot analysis revealed that CpMBF1 was able to activate HIS3 transcription in response to histidine starvation [18].
  • Transformation experiments with circular plasmids carrying a single gene domain demonstrated that the 5' and 3' flanking DNA regions (P and T) of the HIS3 and URA3 genes are preferred as sites for plasmid integration by several fold over the corresponding ORFs [19].

Physical interactions of HIS3

  • Conditions that induce HIS3 and TRP3 transcription result in an altered balance between these complexes strongly in favor of the form without Spt8 [20].
  • GCN4 protein binds specifically to the 20 bp region of the HIS3 gene that is critical for transcriptional regulation in vivo and contains the TGACTC sequence common to coregulated genes [21].
  • We then determined their transcription activation strength using fusions to the Gal4 DNA-binding domain and a His3 reporter gene which contained a promoter with a Gal4-binding site [22].

Enzymatic interactions of HIS3

  • Strains containing a disrupted leu3 allele were constructed by deleting 0.7-kb of LEU3 DNA and inserting the yeast HIS3 gene in its place [23].
  • Mitotic recombination was initiated by HO endonuclease-induced DSBs at the HO cut site (HOcs) located at his3-delta 3'::HOcs, and His+ recombinants were selected [24].

Regulatory relationships of HIS3

  • Of the putative interacting genes examined, PBP1 promoted the highest level of resistance to 3-aminotriazole (>100 mM) in constructs in which HIS3 was used as a reporter [25].
  • We propose that many of the hydrophobic clusters in GCN4 act independently of one another to provide redundant means of stimulating transcription and that the functional contributions of these different segments are cumulative at the HIS3 promoter [26].
  • In addition, we found that NoV RNA1 could support limited replication of a deletion derivative of the heterologous FHV RNA2 that expressed the yeast HIS3 selectable marker, resulting in formation of HIS+ colonies [27].
  • Saccharomyces cerevisiae containing an integrated copy of the HIS3 gene under transcriptional control of a minimal CYC1 promoter and two copies of the rat enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase PPRE was constructed and transformed with a rat liver cDNA yeast expression library [28].
  • A similar association between the Ty transcript level and transpositional activation of his3 delta 4 is obtained in cells expressing GAL1-promoted Ty2-H556 or Ty2-917 elements, but only if the element does not contain a marker [29].

Other interactions of HIS3

  • Both TC and TR support basal HIS3 transcription and require the TATA binding protein TFIID, but only TR responds to transcriptional activation by GCN4 and GAL4 [9].
  • In active genes (URA3, HIS3), photolyase repairs the non-transcribed strand faster than the transcribed strand and can match fast removal of lesions from the transcribed strand by NER (transcription-coupled repair) [30].
  • CDC39, an essential nuclear protein that negatively regulates transcription and differentially affects the constitutive and inducible HIS3 promoters [9].
  • Examining the role of this subunit, we find that C-terminally truncated SPT7 resulted in derepressed HIS3 transcription [31].
  • To identify molecular functions that act downstream of or in parallel with Gcn5 protein, we screened for suppressors that rescue the transcriptional defects of HIS3 caused by a catalytically inactive mutant Gcn5, the E173H mutant [12].

Analytical, diagnostic and therapeutic context of HIS3


  1. Nucleosome loss activates CUP1 and HIS3 promoters to fully induced levels in the yeast Saccharomyces cerevisiae. Durrin, L.K., Mann, R.K., Grunstein, M. Mol. Cell. Biol. (1992) [Pubmed]
  2. Yeast HIS3 expression in Escherichia coli depends upon fortuitous homology between eukaryotic and prokaryotic promoter elements. Struhl, K. J. Mol. Biol. (1986) [Pubmed]
  3. The yeast his3 promoter contains at least two distinct elements. Struhl, K. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  4. Preferential accessibility of the yeast his3 promoter is determined by a general property of the DNA sequence, not by specific elements. Mai, X., Chou, S., Struhl, K. Mol. Cell. Biol. (2000) [Pubmed]
  5. Oxo-vanadium as a spin probe for the investigation of the metal coordination environment of imidazole glycerol phosphate dehydratase. Petersen, J., Hawkes, T.R., Lowe, D.J. J. Inorg. Biochem. (2000) [Pubmed]
  6. The UV response involving the Ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals. Engelberg, D., Klein, C., Martinetto, H., Struhl, K., Karin, M. Cell (1994) [Pubmed]
  7. RNA-mediated recombination in S. cerevisiae. Derr, L.K., Strathern, J.N., Garfinkel, D.J. Cell (1991) [Pubmed]
  8. Negative control at a distance mediates catabolite repression in yeast. Struhl, K. Nature (1985) [Pubmed]
  9. 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]
  10. Mot1 associates with transcriptionally active promoters and inhibits association of NC2 in Saccharomyces cerevisiae. Geisberg, J.V., Moqtaderi, Z., Kuras, L., Struhl, K. Mol. Cell. Biol. (2002) [Pubmed]
  11. Two alternative pathways of transcription initiation in the yeast negative regulatory gene GAL80. Sakurai, H., Ohishi, T., Fukasawa, T. Mol. Cell. Biol. (1994) [Pubmed]
  12. Histone H3 Ser10 phosphorylation-independent function of Snf1 and Reg1 proteins rescues a gcn5- mutant in HIS3 expression. Liu, Y., Xu, X., Singh-Rodriguez, S., Zhao, Y., Kuo, M.H. Mol. Cell. Biol. (2005) [Pubmed]
  13. Cloning and characterization of ERG8, an essential gene of Saccharomyces cerevisiae that encodes phosphomevalonate kinase. Tsay, Y.H., Robinson, G.W. Mol. Cell. Biol. (1991) [Pubmed]
  14. Interstitial telomeres are hotspots for illegitimate recombination with DNA molecules injected into the macronucleus of Paramecium primaurelia. Katinka, M.D., Bourgain, F.M. EMBO J. (1992) [Pubmed]
  15. ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance. Kanazawa, S., Driscoll, M., Struhl, K. Mol. Cell. Biol. (1988) [Pubmed]
  16. Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast. Liu, H., Krizek, J., Bretscher, A. Genetics (1992) [Pubmed]
  17. Restoration of the yeast LEU2 gene by transcriptionally controlled recombination between tandem repeats. Mink, M., Basak, A.N., Küntzel, H. Mol. Gen. Genet. (1990) [Pubmed]
  18. Cryptosporidium parvum: functional complementation of a parasite transcriptional coactivator CpMBF1 in yeast. Zhu, G., LaGier, M.J., Hirose, S., Keithly, J.S. Exp. Parasitol. (2000) [Pubmed]
  19. Targeted DNA integration within different functional gene domains in yeast reveals ORF sequences as recombinational cold-spots. Gjuracic, K., Pivetta, E., Bruschi, C.V. Mol. Genet. Genomics (2004) [Pubmed]
  20. Inhibition of TATA-binding protein function by SAGA subunits Spt3 and Spt8 at Gcn4-activated promoters. Belotserkovskaya, R., Sterner, D.E., Deng, M., Sayre, M.H., Lieberman, P.M., Berger, S.L. Mol. Cell. Biol. (2000) [Pubmed]
  21. GCN4 protein, synthesized in vitro, binds HIS3 regulatory sequences: implications for general control of amino acid biosynthetic genes in yeast. Hope, I.A., Struhl, K. Cell (1985) [Pubmed]
  22. Transcriptional activators in yeast. Titz, B., Thomas, S., Rajagopala, S.V., Chiba, T., Ito, T., Uetz, P. Nucleic Acids Res. (2006) [Pubmed]
  23. Cloning, disruption and chromosomal mapping of yeast LEU3, a putative regulatory gene. Brisco, P.R., Cunningham, T.S., Kohlhaw, G.B. Genetics (1987) [Pubmed]
  24. Expression of Saccharomyces cerevisiae MATa and MAT alpha enhances the HO endonuclease-stimulation of chromosomal rearrangements directed by his3 recombinational substrates. Fasullo, M., Bennett, T., Dave, P. Mutat. Res. (1999) [Pubmed]
  25. Pbp1p, a factor interacting with Saccharomyces cerevisiae poly(A)-binding protein, regulates polyadenylation. Mangus, D.A., Amrani, N., Jacobson, A. Mol. Cell. Biol. (1998) [Pubmed]
  26. Identification of seven hydrophobic clusters in GCN4 making redundant contributions to transcriptional activation. Jackson, B.M., Drysdale, C.M., Natarajan, K., Hinnebusch, A.G. Mol. Cell. Biol. (1996) [Pubmed]
  27. Nodamura virus RNA replication in Saccharomyces cerevisiae: heterologous gene expression allows replication-dependent colony formation. Price, B.D., Eckerle, L.D., Ball, L.A., Johnson, K.L. J. Virol. (2005) [Pubmed]
  28. Identification of COUP-TFII as a peroxisome proliferator response element binding factor using genetic selection in yeast: COUP-TFII activates transcription in yeast but antagonizes PPAR signaling in mammalian cells. Marcus, S.L., Capone, J.P., Rachubinski, R.A. Mol. Cell. Endocrinol. (1996) [Pubmed]
  29. Ty RNA levels determine the spectrum of retrotransposition events that activate gene expression in Saccharomyces cerevisiae. Curcio, M.J., Hedge, A.M., Boeke, J.D., Garfinkel, D.J. Mol. Gen. Genet. (1990) [Pubmed]
  30. Chromatin structure modulates DNA repair by photolyase in vivo. Suter, B., Livingstone-Zatchej, M., Thoma, F. EMBO J. (1997) [Pubmed]
  31. SALSA, a variant of yeast SAGA, contains truncated Spt7, which correlates with activated transcription. Sterner, D.E., Belotserkovskaya, R., Berger, S.L. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  32. Cloning and sequence analysis of the Pichia pastoris TRP1, IPP1 and HIS3 genes. Cosano, I., Alvarez, P., Molina, M., Nombela, C. Yeast (1998) [Pubmed]
  33. Sticky-end polymerase chain reaction method for systematic gene disruption in Saccharomyces cerevisiae. Maftahi, M., Gaillardin, C., Nicaud, J.M. Yeast (1996) [Pubmed]
  34. Molecular cloning and sequence analysis of the Zygosaccharomyces bailii HIS3 gene encoding the imidazole glycerolphosphate dehydratase. Branduardi, P. Yeast (2002) [Pubmed]
  35. Purification and characterization of the imidazoleglycerol-phosphate dehydratase of Saccharomyces cerevisiae from recombinant Escherichia coli. Hawkes, T.R., Thomas, P.G., Edwards, L.S., Rayner, S.J., Wilkinson, K.W., Rice, D.W. Biochem. J. (1995) [Pubmed]
  36. Electroporation-stimulated recombination in yeast. Higgins, D.R., Strathern, J.N. Yeast (1991) [Pubmed]
WikiGenes - Universities