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Gene Review

HIS4  -  trifunctional histidinol...

Saccharomyces cerevisiae S288c

Synonyms: Histidine biosynthesis trifunctional protein, YCL030C, YCL183, YCL30C
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Disease relevance of HIS4


High impact information on HIS4

  • However, the SSL2 suppressor gene does not restore HIS4 expression by removal of the stem-loop from DNA or the mRNA [5].
  • A suppressor of a HIS4 transcriptional defect encodes a protein with homology to the catalytic subunit of protein phosphatases [6].
  • A yeast protein, Sui3, isolated as an extragenic suppressor of his4 initiation codon mutations, exhibits extensive sequence identity with human eIF-2 beta, especially in the polylysine and zinc finger domains, thereby reinforcing the view that these elements are important for function [7].
  • To test this hypothesis, we have taken advantage of two mutations constructed previously in the UACUAAC box of an actin-HIS4 fusion [8].
  • Under inducing conditions, a significant number of tetrads were formed that had undergone gene conversions in favor of the HIS4+ allele [9].

Biological context of HIS4


Anatomical context of HIS4


Associations of HIS4 with chemical compounds


Physical interactions of HIS4

  • Direct biochemical analysis shows that the BAS2 gene encodes a protein that binds to both the HIS4 and PHO5 promoters [10].
  • It was shown previously that mutation of the Rap1p binding site in the HIS4 promoter causes a similar effect on HIS4 expression and that this promoter mutation also causes a change in chromatin structure [22].

Regulatory relationships of HIS4

  • The ability of spt2 mutations to suppress the transcriptional interference caused by the delta promoter insertion his-4-912 delta correlates with an increase in wild-type HIS4 mRNA levels [23].
  • The predicted presence of large helical structural variation in yeast HIS4 upstream region is correlated with general amino acid control on the CYC1 gene [24].
  • BAS1 has a Myb motif and activates HIS4 transcription only in combination with BAS2 [25].
  • We now show that wild-type Gcn4 requires the TATA element for correct messenger RNA start-site selection, but Gcn4 derivatives with deletions in the activation domain activate HIS4 transcription at the correct mRNA start site (I) in the absence of the TATA element [26].
  • Compared to recombinants isolated from control strains that lack HOT1, HOT1-promoted His+ recombinants are more often homozygous for sequences distal to HIS4 [27].

Other interactions of HIS4

  • An act3 mutation also affects expression of the HIS4 and LYS2 genes; thus, Act3p is not a delta element-specific transcriptional regulator [11].
  • SSL1, a suppressor of a HIS4 5'-UTR stem-loop mutation, is essential for translation initiation and affects UV resistance in yeast [28].
  • The Saccharomyces cerevisiae SPT2 gene was identified by genetic screens for mutations which are suppressors of Ty and delta insertional mutations at the HIS4 locus [23].
  • Second, in contrast to not mutations, mutations in MOT1 decreased HIS3 and HIS4 TATA-less transcription [29].
  • Three Tn10LUK insertion mutations in the SEP1 gene were characterized. sep1 mutants grew more slowly than wild-type cells, showed a two- to fivefold decrease in the rate of spontaneous mitotic recombination between his4 heteroalleles, and were delayed in their ability to return to growth after UV or gamma irradiation [30].

Analytical, diagnostic and therapeutic context of HIS4


  1. Regulation of HIS4-lacZ fusions in Saccharomyces cerevisiae. Silverman, S.J., Rose, M., Botstein, D., Fink, G.R. Mol. Cell. Biol. (1982) [Pubmed]
  2. Cloning and characterization of the multifunctional his-3 gene of Neurospora crassa. Legerton, T.L., Yanofsky, C. Gene (1985) [Pubmed]
  3. Genetic events associated with an insertion mutation in yeast. Chaleff, D.T., Fink, G.R. Cell (1980) [Pubmed]
  4. Stable chromosomal integration of the entire nitrogen fixation gene cluster from Klebsiella pneumoniae in yeast. Zamir, A., Maina, C.V., Fink, G.R., Szalay, A.A. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  5. SSL2, a suppressor of a stem-loop mutation in the HIS4 leader encodes the yeast homolog of human ERCC-3. Gulyas, K.D., Donahue, T.F. Cell (1992) [Pubmed]
  6. A suppressor of a HIS4 transcriptional defect encodes a protein with homology to the catalytic subunit of protein phosphatases. Arndt, K.T., Styles, C.A., Fink, G.R. Cell (1989) [Pubmed]
  7. Structure of the beta subunit of translational initiation factor eIF-2. Pathak, V.K., Nielsen, P.J., Trachsel, H., Hershey, J.W. Cell (1988) [Pubmed]
  8. Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA. Parker, R., Siliciano, P.G., Guthrie, C. Cell (1987) [Pubmed]
  9. Double-strand breaks can initiate meiotic recombination in S. cerevisiae. Kolodkin, A.L., Klar, A.J., Stahl, F.W. Cell (1986) [Pubmed]
  10. Multiple global regulators control HIS4 transcription in yeast. Arndt, K.T., Styles, C., Fink, G.R. Science (1987) [Pubmed]
  11. Epigenetic effects on yeast transcription caused by mutations in an actin-related protein present in the nucleus. Jiang, Y.W., Stillman, D.J. Genes Dev. (1996) [Pubmed]
  12. GTP hydrolysis controls stringent selection of the AUG start codon during translation initiation in Saccharomyces cerevisiae. Huang, H.K., Yoon, H., Hannig, E.M., Donahue, T.F. Genes Dev. (1997) [Pubmed]
  13. The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Leeds, P., Peltz, S.W., Jacobson, A., Culbertson, M.R. Genes Dev. (1991) [Pubmed]
  14. Mutations in the structural genes for eukaryotic initiation factors 2 alpha and 2 beta of Saccharomyces cerevisiae disrupt translational control of GCN4 mRNA. Williams, N.P., Hinnebusch, A.G., Donahue, T.F. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  15. tRNAi(met) functions in directing the scanning ribosome to the start site of translation. Cigan, A.M., Feng, L., Donahue, T.F. Science (1988) [Pubmed]
  16. Probing the membrane topology of Candida tropicalis cytochrome P450. Sanglard, D., Sengstag, C., Seghezzi, W. Eur. J. Biochem. (1993) [Pubmed]
  17. Functional expression of the transcriptional activator Opaque-2 of Zea mays in transformed yeast. Mauri, I., Maddaloni, M., Lohmer, S., Motto, M., Salamini, F., Thompson, R., Martegani, E. Mol. Gen. Genet. (1993) [Pubmed]
  18. Transformation of Candida oleophila and survival of a transformant on orange fruit under field conditions. Chand-Goyal, T., Eckert, J.W., Droby, S., Glickmann, E., Atkinson, K. Curr. Genet. (1999) [Pubmed]
  19. Signaling through regulated transcription factor interaction: mapping of a regulatory interaction domain in the Myb-related Bas1p. Pinson, B., Kongsrud, T.L., Ording, E., Johansen, L., Daignan-Fornier, B., Gabrielsen, O.S. Nucleic Acids Res. (2000) [Pubmed]
  20. A trans-acting suppressor restores splicing of a yeast intron with a branch point mutation. Couto, J.R., Tamm, J., Parker, R., Guthrie, C. Genes Dev. (1987) [Pubmed]
  21. Transposable element sequences involved in the enhancement of yeast gene expression. Roeder, G.S., Rose, A.B., Pearlman, R.E. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  22. Regulation of HIS4 expression by the Saccharomyces cerevisiae SIN4 transcriptional regulator. Jiang, Y.W., Stillman, D.J. Genetics (1995) [Pubmed]
  23. Mutational and functional analysis of dominant SPT2 (SIN1) suppressor alleles in Saccharomyces cerevisiae. Lefebvre, L., Smith, M. Mol. Cell. Biol. (1993) [Pubmed]
  24. The predicted presence of large helical structural variation in yeast HIS4 upstream region is correlated with general amino acid control on the CYC1 gene. Nussinov, R. J. Biomol. Struct. Dyn. (1985) [Pubmed]
  25. BAS1 has a Myb motif and activates HIS4 transcription only in combination with BAS2. Tice-Baldwin, K., Fink, G.R., Arndt, K.T. Science (1989) [Pubmed]
  26. TATA-dependent and TATA-independent transcription at the HIS4 gene of yeast. Pellman, D., McLaughlin, M.E., Fink, G.R. Nature (1990) [Pubmed]
  27. A chromosome containing HOT1 preferentially receives information during mitotic interchromosomal gene conversion. Voelkel-Meiman, K., Roeder, G.S. Genetics (1990) [Pubmed]
  28. SSL1, a suppressor of a HIS4 5'-UTR stem-loop mutation, is essential for translation initiation and affects UV resistance in yeast. Yoon, H., Miller, S.P., Pabich, E.K., Donahue, T.F. Genes Dev. (1992) [Pubmed]
  29. The NOT, SPT3, and MOT1 genes functionally interact to regulate transcription at core promoters. Collart, M.A. Mol. Cell. Biol. (1996) [Pubmed]
  30. Molecular and genetic analysis of the gene encoding the Saccharomyces cerevisiae strand exchange protein Sep1. Tishkoff, D.X., Johnson, A.W., Kolodner, R.D. Mol. Cell. Biol. (1991) [Pubmed]
  31. Mutations at a Zn(II) finger motif in the yeast eIF-2 beta gene alter ribosomal start-site selection during the scanning process. Donahue, T.F., Cigan, A.M., Pabich, E.K., Valavicius, B.C. Cell (1988) [Pubmed]
  32. Efficient translation of poly(A)-deficient mRNAs in Saccharomyces cerevisiae. Proweller, A., Butler, S. Genes Dev. (1994) [Pubmed]
  33. Nucleosome fractionation by mercury affinity chromatography. Contrasting distribution of transcriptionally active DNA sequences and acetylated histones in nucleosome fractions of wild-type yeast cells and cells expressing a histone H3 gene altered to encode a cysteine 110 residue. Chen, T.A., Smith, M.M., Le, S.Y., Sternglanz, R., Allfrey, V.G. J. Biol. Chem. (1991) [Pubmed]
  34. Kluyveromyces lactis HIS4 transcriptional regulation: similarities and differences to Saccharomyces cerevisiae HIS4 gene. Lamas-Maceiras, M., Cerdán, M.E., Freire-Picos, M.A. FEBS Lett. (1999) [Pubmed]
  35. The use of iodinated antibody in immunodiffusion analysis to detect yeast nonsense termination fragments. Bigelis, R., Fink, G.R. J. Immunol. Methods (1978) [Pubmed]
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