Disease relevance of CYC1

• Saccharomyces cerevisiae iso-1-cytochrome c has been expressed in Escherichia coli by coexpression of the genes encoding the cytochrome (CYC1) and yeast cytochrome c heme lyase (CYC3) [1].
• By selective attachment of a DNA cleavage agent to specific residues in the yeast TATA box binding protein (yTBP), we demonstrate that, in solution, yTBP binds to the TATA boxes of both the adenovirus major late promoter and the yeast CYC1 promoter with only a modest preference in orientation and binds well to several overlapping binding sites [2].
• Despite this specificity, TFIID also binds with high affinity to several TATA elements that do not match the consensus TATA sequences (TATAAA and TATATA): the yeast LEU2 TATA (TATTATTTA), the simian virus 40 TATA (CTTATTTAT), and the yeast CYC1 -10 TATA (TTATACATT) all bound TFIID [3].
• The Moraxella sp. strain B gene dehH1, encoding fluoroacetate dehalogenase, was placed under the control of both the GPD1 and CYC1 promoters [4].
• Comparison of expression of the endo-beta-1,3-1,4-glucanase gene from Bacillus subtilis in Saccharomyces cerevisiae from the CYC1 and ADH1 promoters [5].

High impact information on CYC1

• A similar effect was found at the ADH1 locus, establishing that this effect is not cyc1 gene-specific [6].
• Mutations in the Saccharomyces cerevisiae SUA7 gene were isolated as suppressors of an aberrant ATG translation initiation codon in the leader region of the cyc1 gene [6].
• Strikingly, this sequence bears no obvious similarity to the sequence bound by HAP1 at UAS1 of the CYC1 gene [7].
• Transcriptional activation by the yeast CYC1 upstream activation site UAS2UP1 requires the products of both the HAP2 and HAP3 regulatory genes [8].
• 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 [9].

Chemical compound and disease context of CYC1

• Different CYC1 alleles can be conveniently recovered by digestion of total DNA from transformed strains with BgI II, a restriction endonuclease that does not cut the vector or the CYC1 gene, followed by transformation of Escherichia coli, selecting the ampicillin resistance gene carried on the original vector [10].
• The reporter gene contained two copies of a progesterone response element upstream of the yeast proximal CYC1 promoter fused to the beta-galactosidase gene of Escherichia coli [11].

Biological context of CYC1

• A GAL4-like zinc finger (residues 1-148) specifies binding to the dissimilar sites UAS1 (of CYC1) and CYC7, and an acidic domain (residues 1307-1483) is essential for activation of transcription [12].
• This study investigates the overproduction of the CYP1 protein when the CYP1(HAP1) gene is placed under the control of the GAL10-CYC1 hybrid promoter (either at the locus of the CYP1(HAP1) gene or cloned in a high-copy-number plasmid) [13].
• Although both CYC1 and CYC7 mRNAs are substantially lowered after growth in glucose medium, there is a difference in the kinetics of glucose derepression [14].
• CYC1 and sup4 are part of a tightly linked cluster of genes on chromosome X in the yeast Saccharomyces cerevisiae [15].
• The physical mapping has allowed unambiguous determination of the orientation of CYC1 and sup4 relative to each other, the centromere, and a nearby transfer ribonucleic acid (tRNA(2Ser)) gene [15].

Anatomical context of CYC1

• However, in contrast to the normal CYC1+ mRNA that is associated mainly with four to seven ribosomes, the bulk of the CYC1-239-O mRNA is associated with one to four ribosomes [16].
• CYC1 mRNA distribution on polyribosomes confirmed that only ATG codons within the initiation region were translated at high efficiency [17].
• Current work on degradation of proteins in mitochondria, on degradation of mRNA in the nucleus, and on N-terminal acetylation stems from properties of CYC1 mutants isolated in early screens more than a decade ago [18].

Associations of CYC1 with chemical compounds

• For others (COX5a and CYC1) the level of expression is nearly constant between 200 microM O2 and their threshold and then drops off [19].
• The mutated phenotype that commutes the expression of the two isocytochrome structural genes (superactivation of CYP3 and inhibition of CYC1) results from a transversion in an AGT codon (serine) in the wild-type to an AGG codon (arginine) in the mutant [20].
• 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 [21].
• NMR analysis of CYP1(HAP1) DNA binding domain-CYC1 upstream activation sequence interactions: recognition of a CGG trinucleotide and of an additional thymine 5 bp downstream by the zinc cluster and the N-terminal extremity of the protein [22].
• Attempts to increase production by addition of IPTG suppressed the number of copies of the CYC1 gene within the population [1].

Physical interactions of CYC1

• First, while CYC1 contains two sites that bind HAP1 cooperatively, CYT1 has a single high-affinity site [23].
• The binding of HAP1 to the CYT1 element was studied in detail and found to differ in two important respects from binding to the CYC1 element [23].
• When oligonucleotides containing a REB1-binding site are placed between the CYC1 upstream activating sequence and TATA box, transcription by RNA polymerase II in vivo is substantially reduced, suggesting that REB1 acts as a repressor of RNA polymerase II transcription [24].
• The ABF1 binding sites also acted in an orientation-independent manner when a synthetic ABF1 binding site was inserted into the yeast CYC1 gene lacking its transcriptional activation region [25].
• A LexA-Gln3 fusion protein supported transcriptional activation when bound to one or more LexAp binding sites upstream of a minimal CYC1-derived promoter devoid of UAS elements [26].

Regulatory relationships of CYC1

• The CYC1 gene of Saccharomyces cerevisiae is positively regulated by the HAP2 and HAP3 proteins, which form a heteromeric complex that binds to a CCAAT box in the upstream activation site, UAS2, and which activate transcription in a nonfermentable carbon source [27].
• The predicted presence of large helical structural variation in yeast HIS4 upstream region is correlated with general amino acid control on the CYC1 gene [28].
• Hap1 is a yeast transcriptional activator which controls expression of genes such as CYC1 and CYC7 [29].
• The ENO1 URS element repressed transcription of the yeast CYC1 gene when positioned between the CYC1 upstream activation sequences (UAS elements) and TATAAA boxes [30].
• The ROX1 locus of S. cerevisiae is known to regulate CYC1, COXVb, and ANB1 genes at the transcriptional level; the ROX1 locus thus regulates all known anaerobically expressed genes that are involved in different cellular functions such as respiration and protein synthesis [31].

Other interactions of CYC1

• The expression of the yeast CYC1 and CYC7 genes is controlled by the HAP1 activator [12].
• The TFIIB mutations conferred downstream shifts in transcription initiation at the ADH1 and CYC1 promoters, whereas no significant shifts were observed at the HIS3 promoter [32].
• Nonetheless, essential signals have seemed to be confined to compact regions in vivo, and we find that a short RNA with only 70 bases of GAL7 sequence upstream and 8 to 10 bases downstream of the poly(A) addition site is processed in vitro, as is an analogous CYC1 pre-RNA [33].
• In an ssn6 mutant genetic background, both COX6 and CYC1 were expressed constitutively at high levels in repressing media [34].
• The mutator gene DEL1 in the yeast Saccharomyces cerevisiae causes a high rate of formation of multisite mutations that encompass the following three adjacent genes: CYC1, which determines the structure of iso-1-cytochrome c; RAD7, which controls UV sensitivity; and OSM1, which controls osomotic sensitivity [35].

Analytical, diagnostic and therapeutic context of CYC1

• Ligation of the 18 bp element into a plasmid carrying the CYC1 promoter deleted UAS-activated transcription and conferred transcriptional repression by unsaturated fatty acids [36].
• CAR1 DNA fragments containing the yeast CAR1 gene sequences from the transcription initiation site (-49) or translation initiation site (+1) to the +501 region were amplified using PCR and inversely fused to the yeast CYC1 promoter on the yeast YIp5 plasmid [37].
• Dissection of the upstream activation site 1 (UAS1) of the yeast CYC1 gene showed that the A and B regions respond individually to regulation by the HAP1 protein, and that a point mutation in the B region converts this region to a translation upstream factor (TUF)-regulated element [38].
• Site-directed mutagenesis in and adjacent to the 38-bp region was used to identify signals involved in the formation and positioning of CYC1 mRNA 3' ends [39].
• Yeast cytochrome c messenger RNA. In vitro translation and specific immunoprecipitation of the CYC1 gene product [40].

References