Disease relevance of HIS4

• The beginning of the Saccharomyces cerevisiae HIS4 gene has been fused to the structural gene for Escherichia coli beta-galactosidase [1].
• The protein shows two regions of homology to the yeast HIS4 gene which correspond to the hisIE and hisD genes of Escherichia coli and Salmonella typhimurium [2].
• In each of these classes of revertants, the his4 region is closely linked to the chromosomal aberration [3].
• A bacterial plasmid containing the entire nitrogen fixation (nif) gene cluster (consisting of at least 15 genes) from Klebsiella pneumoniae was used in conjunction with an Escherichia coli-yeast shuttle plasmid containing the yeast his4 gene cluster to cotransform a his4- recipient strain of Saccharomyces cerevisiae [4].

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

• One of these, general amino acid control, involves a DNA binding protein, GCN4, that stimulates transcription in response to amino acid starvation by binding to 5'-TGACTC-3' sequences in the HIS4 promoter region [10].
• Gene inactivation can result when a delta element of the Ty1 transposon inserted into the yeast HIS4 promoter (his4-912delta) alters the transcription initiation site [11].
• We have isolated and characterized two suppressor genes, SUI4 and SUI5, that can initiate translation in the absence of an AUG start codon at the HIS4 locus in Saccharomyces cerevisiae [12].
• In the absence of UPF1 function, frameshift or nonsense mutations in the HIS4 or LEU2 genes that normally cause rapid mRNA decay fail to have this effect [13].
• We show that the latter phenotype exists because the SUI mutations elevate expression of GCN4, an activator of HIS4 transcription [14].

Anatomical context of HIS4

• The mutant transfer RNA also directed the ribosome to initiate at an AGG placed in the upstream region of the his4 message [15].
• Depending on the localization of invHIS4C on the endoplasmic reticulum (ER) cytoplasmic or luminal side, the enzyme converts histidinol to histidine and allows the his4 yeast strain to grow on histidinol-supplemented medium [16].

Associations of HIS4 with chemical compounds

• It was shown that the O2 protein is able to trans-activate the HIS4 promoter in yeast cells and binds to it in vitro [17].
• Histidine auxotrophs of wild-type strain I-182 of Candida oleophila, produced using ethyl methanesulfonate, were transformed with plasmids containing the HIS3, HIS4 and HIS5 genes of Saccharomyces cerevisiae [18].
• On HIS4 efficient promoter binding and derepression required both factors and adenine limitation [19].
• We showed previously that the transcript from an actin-HIS4 gene fusion containing the mutation TACTAAC to TACTACC (designated C259) is spliced inefficiently, thereby preventing growth on the histidine precursor histidinol [20].
• Ty917 prevents HIS4 transcription, thus rendering the cell histidine requiring [21].

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

• Protein sequence analysis shows that a mutant beta-subunit allows initiation at a UUG codon in the absence of an AUG start codon at HIS4 [31].
• Northern blot analysis revealed the disappearance of some mRNAs (CYH2 and HIS4) consistent with a role for poly(A) tails in mRNA stability [32].
• A technique for the separation of transcriptionally active and inactive nucleosomes by mercury affinity chromatography has been applied to study the nucleosomal distribution of DNA sequences from the GAL1, ACT1, HIS4, MAT alpha, and HMRa genes of yeast [33].
• Sequence analysis of the Kluyveromyces lactis HIS4 (KlHIS4) gene promoter reveals relevant differences in comparison to the Saccharomyces cerevisiae HIS4 homologous gene [34].
• An autoradiographed immunodiffusion pattern reveals distinct radio-labeled precipitation lines for an extract of yeast with wild type HIS4 protein and for extracts of mutants containing HIS4 nonsense fragments [35].

References