Disease relevance of Pgk1

• Desferrioxamine induction of VEGF and PGK-1 genes was reduced in the ARNT-deficient cells, but at difference with hypoxia, it was not completely suppressed [1].
• Hypoxia induces a 10-fold accumulation of phosphoglycerate kinase 1 mRNA in wild type mouse hepatoma (Hepa 1c1c7) cells; the induction mechanism is Arnt dependent because induction does not occur in Arnt-defective cells [2].
• To examine the role of placenta growth factor (PlGF) in the pathogenesis of pulmonary emphysema, we generated PlGF-transgenic (TG) mice using a phosphoglycerate kinase promoter [3].
• The regulatory sequences of the Pgk-1 gene were used to drive the E. coli lacZ reporter gene and 2 strains of transgenic animals created with this Pgk-lacZ transgene carried on autosomes [4].
• Using the P19 embryonal carcinoma cells as recipients, we found that constructs carrying the promoter and intragenic regions of the murine Pgk-1 gene were expressed with high efficiency [5].

High impact information on Pgk1

• To further our understanding of initiation and imprinting of X-chromosome inactivation, we have examined methylation of specific CpG sites of X-linked Pgk-1 and G6pd genes throughout female mouse development [6].
• Methylation occurs around the time of inactivation and earlier for Pgk-1, which is closer to the X-inactivation centre [6].
• Following hybrid formation, the chronology of X chromosome replication and the expression of X-linked gene Pgk-1 indicated that all X chromosomes contributed by both parents were active in these hybrids [7].
• We have induced teratocarcinomas from female embryos heterozygous for electrophoretic variants of the X-linked gene coding for phosphoglycerate kinase (PGK) [8].
• Plasma of mice bearing fibrosarcoma tumours contained several-fold more phosphoglycerate kinase, as compared with mice without tumours [9].

Chemical compound and disease context of Pgk1

• Gene expression of known HIF targets phosphoglycerate kinase (PGK), vascular endothelial growth factor (VEGF) and glucose transporter-1 (GLUT-1) increased under hypoxia, but was reduced in the HIF null cultures [10].
• In vitro induction of GAL4/TATA by coinfection of cells with adenovirus expressing the GAL4/VP16 fusion protein (Ad/3-phosphoglycerate kinase (PGK)-GV16) was dose-dependent and reached as high as 4 x 10(4)- to 9 x 10(4)-fold above basal levels when GAL4/TATA and GAL4/VP16 were delivered at a ratio of 10:1 [11].
• We have identified a gene in Vibrio cholerae (epd) which encodes an erythrose-4-phosphate dehydrogenase activity and is located immediately downstream of an iron-regulated virulence gene, irgA, and immediately upstream of a gene encoding phosphoglycerate kinase (pgk) [12].
• Three promoters have been tested driving the cysteine synthesis genes: two general promoters, the Rous sarcoma virus long terminal repeat and mouse phosphoglycerate kinase promoter, and a rumen-specific promoter from the sheep small proline-rich protein gene [13].

Biological context of Pgk1

• Pgk1 and Hprt gene activity in the peri-implantation mouse embryo is influenced by the parental origin of the X-chromosome [14].
• Like the Pgk1 locus, significantly more maternal Hprt transcripts were found in the gastrula-stage embryos irrespective of their genotypes [14].
• A factor stimulating transcription of the testis-specific Pgk-2 gene recognizes a sequence similar to the binding site for a transcription inhibitor of the somatic-type Pgk-1 gene [15].
• Comparative mapping data from the human X chromosome indicate that the most probable location of the mouse X-inactivation center is distal to Ccg-1 and in the region of the Pgk-1 locus [16].
• Tissue-specific expression of the two PGK-encoding genes (Pgk) seems to be transcriptionally controlled, since tissue distribution of the mRNAs coincides well with that of the proteins [17].

Anatomical context of Pgk1

• Pgk1 mRNA abundance was severely reduced in androgenones at the eight-cell and morula stages and remained reduced, but to a lesser degree, in androgenetic blastocysts [18].
• For the Pgk1 gene, the maternal allele-specific transcripts were consistently more abundant than the paternal transcripts in the blastocyst and the late gastrula [14].
• A transient expression assay of DNAs having various portions of the Pgk-2 upstream region linked to the chloramphenicol acetyltransferase (CAT)-encoding gene (cat) was performed using mouse cell lines that exclusively express Pgk-1 [17].
• Moreover, the cis element inhibited Pgk-2 transcription with no effect on Pgk-1 transcription in a cell-free system using nuclear extracts of rat liver [17].
• The expression of maternally derived X-chromosomal Pgk-1 alleles was investigated in oocytes and early embryos of mice carrying different alleles (Xcea, Xcec) of the X-chromosome controlling element (Xce) locus [19].

Associations of Pgk1 with chemical compounds

• We sought to determine whether the paternal allele of the X chromosome-linked gene for 3-phosphoglycerate kinase 1 (Pgk-1), which is located very near the center of X chromosome inactivation, is transcribed prior to differentiation of extraembryonic lineages [20].
• The promoter for the phosphoglycerate kinase 1 (PGK1) gene contains an initiator element, but no TATA sequence, whereas the promoter for the glucose transporter 1 (Glut1) gene contains a TATA element but no initiator sequence [21].
• The hypothesis that codon bias is related to expression level is shown not to hold for the Pgk genes; however, the idea that a deficiency of TA and CG dinucleotides and an excess of TG and CT dinucleotides contributes to codon bias is supported [22].
• Phosphoglycerate kinase (PGK, EC 2.7.2.3), which is expressed specifically in sperm and spermatids, is an enzyme in the Embden-Meyerhof pathway that converts glucose to pyruvate [23].
• For mouse Pgk-1, previous restriction enzyme analysis had shown apparently complete methylation of only one cytosine in the promoter region on the Xi, at HpaII site H7, which is located in the untranslated region, 28 nucleotides upstream of the translation start site [24].

Regulatory relationships of Pgk1

• Therefore, we conclude that the maternal PGK-1 locus is already activated during late preimplantation development whereas the paternally inherited gene locus remains silent at the preimplantation stage but is subsequently expressed at approximately the time of X-chromosomal inactivation [25].

Other interactions of Pgk1

• Using quantitative oligonucleotide hybridization assays after RT-PCR, we investigated Xist expression in ES lines heterozygous at the Pgk-1 and Xist loci [26].
• We report the assignment of two new loci, EM13 and DXSmh44, to the Ccg-1/Pgk-1 interval [16].
• Linkage analysis involving the markers Pgk-1 and Ags indicated a gene order of centromere--Hprt--Pgk-1--Ags in crosses involving both stocks of wild mice [27].
• This finding also demonstrates that the timing of reactivation of maternal Pgk-1 is not influenced by the Xce locus [19].
• To help resolve this issue, we analysed XCI in embryos which carry the T(X;16)16H (Searle's) translocation and are heterozygous at the X-linked Hprt and Pgk-1 genes [28].

Analytical, diagnostic and therapeutic context of Pgk1

• In order to elucidate the mechanistic interpretations underlying differential expression of the two phosphoglycerate kinase (PGK) genes during mammalian spermatogenesis, localization of its mRNAs in mouse testis sections was determined by in situ hybridization [29].
• We have used genomic sequencing aided by ligation-mediated PCR (LMPCR) to assay for 5-methylcytosine in the CpG-rich promoter region of the mouse X-linked phosphoglycerate kinase gene (Pgk-1) [24].
• The two allelic isozymes (wild-type 1B and the electrophoretic variant 1A) of mouse X-linked phosphoglycerate kinase (PGK-1) have been purified by affinity chromatography [30].
• Hybrid selection, in vitro translation with product identification by 2-D gel electrophoresis demonstrated that the PGK-1 cDNA clone hybridized to PGK-2 mRNA in mouse testes [31].
• However, transplantation of cultured cells from 2 of these sarcomas resulted in tumors with single-enzyme PGK phenotypes [32].

References