Disease relevance of GCR1

• In vivo analysis, using isogenic strains of yeast and Escherichia coli transformed with plasmid DNAs, confirmed the binding of both the trans-acting factor RAP1 and the transcriptional activator GCR1 to cis-acting recognition sites located within the PYK UAS element [1].

High impact information on GCR1

• In Saccharomyces cerevisiae, efficient expression of glycolytic and translational component genes requires two DNA binding proteins, RAP1 (which binds to UASRPG) and GCR1 (which binds to the CT box) [2].
• Full-length Rap1p and the amino- and carboxyl-truncated versions of Rap1p were each able to facilitate binding of Gcr1p at an appropriately spaced binding site [3].
• GCR1 gene function is required for high-level glycolytic gene expression [4].
• In this report, I demonstrate that GCR1 encodes a DNA binding protein whose ability to bind DNA is dependent on the CTTCC sequence motif [4].
• Synthetic oligonucleotides, modeled on the UAS element of PYK1, in which the relative positions of the Rap1p- and Gcr1p-binding sites were varied prepared and tested for their ability to function as UAS elements [5].

Biological context of GCR1

• Binding sites for the global regulatory protein known as repressor activator protein 1 (RAP1)/general regulatory factor 1 (GRF1)/translation upstream factor (TUF) are found in close proximity to one or more CTTCC sequence motifs in the controlling region of GCR1-dependent genes [4].
• A complex regulatory element from the yeast gene ENO2 modulates GCR1-dependent transcriptional activation [6].
• We show that, in addition to these factors, expression of SUC2 is affected by mutations in the gene GCR1 that encodes the glycolysis regulatory protein Gcr1p [7].
• A series of in vivo G methylation protection experiments of the native TPI promoter were carried out with wild-type and gcr1 deletion mutant strains [8].
• However, mutating both GCR1-binding sites resulted in a 68-fold reduction in the level of expression of the reporter gene [9].

Anatomical context of GCR1

• Deficiency in GCR1 leads to a pleiotropic phenotype that includes the constitutive presence of peroxisomes and peroxisomal enzymes in glucose-grown cells [10].

Associations of GCR1 with chemical compounds

• The GCR1 gene product is required for maximal transcription of yeast glycolytic genes and for growth of yeast strains in media containing glucose as a carbon source [11].
• Ethanol, sucrose, and maltose continue to repress peroxisomes and peroxisomal enzymes normally and therefore, appear to have GCR1-independent repression mechanisms in H. polymorpha [10].
• A mutant deleted for the GCR1 gene was additionally deficient in fructose repression [10].
• The results obtained describe how the cells respond to different irradiation conditions by modulating important gene classes, including those associated with stress defense, ribosomal proteins, histones, ergosterol and GCR1-controlled sugar metabolism [12].
• Screening of a mutagenized strain carrying a multicopy ENO1-'lacZ fusion plasmid revealed a new mutation affecting most glycolytic enzyme activities in a pattern resembling that caused by gcr1: levels in the range of 10% of wild-type levels on glycerol plus lactate but somewhat higher on glucose [13].

Physical interactions of GCR1

• In this report we show by in vivo footprinting that the regulatory factor encoded by GCR1 binds to two elements in the 3' half of the PGK UAS [14].
• Gcr1p is a DNA binding transcription factor that requires Gcr2p for its functions [15].

Regulatory relationships of GCR1

• Together with use of the two-hybrid system of Fields and Song, they show that Gcr1p in its N-terminal half has a potential transcriptional activating function as well as elements for interaction with Gcr2p, which perhaps acts normally to expose an otherwise cryptic activation domain on Gcr1p [16].
• DNA gel mobility shift assays and in-vitro DNase I protection experiments mapped a DNA binding site for Gcr1p in the transcriptional control region of the SUC2 gene, next to a previously mapped Mig1p binding site [7].
• The GCR1 requirement for yeast glycolytic gene expression is suppressed by dominant mutations in the SGC1 gene, which encodes a novel basic-helix-loop-helix protein [11].
• Transcription of the HXT4 gene is regulated by Gcr1p and Gcr2p in the yeast S. cerevisiae [17].
• Furthermore, we find that Gcr1p positively influences PGK transcription, although it is not responsible for the carbon source dependent regulation of PGK mRNA synthesis [14].

Other interactions of GCR1

• Fairly homologous regions were found between Gcr2 and Gcr1 proteins [18].
• The GCR1 gene encodes a positive transcriptional regulator of the enolase and glyceraldehyde-3-phosphate dehydrogenase gene families in Saccharomyces cerevisiae [19].
• Mutations in GCR1 affect SUC2 gene expression in Saccharomyces cerevisiae [7].
• Dominant mutations in two genes, SGC1 and SGC2, as well as recessive mutations in the SGC5 gene were identified as suppressors of the growth and transcriptional defects caused by a gcr1 null mutation [11].
• A null mutant carrying a deletion of 90% of the GCR1 coding sequence and a URA3 gene insertion was constructed by gene replacement [19].

Analytical, diagnostic and therapeutic context of GCR1

• We carried out a molecular dissection of Rap1p to identify domains contributing to its ability to facilitate binding of Gcr1p [3].
• Using DNA microarrays, the genomic expression patterns of wild-type and gcr1 mutant yeast growing on various media, with and without glucose, were compared [20].

References