Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1991 Oct 25;19(20):5755–5761. doi: 10.1093/nar/19.20.5755

The mouse Pgk-1 gene promoter contains an upstream activator sequence.

M W McBurney 1, L C Sutherland 1, C N Adra 1, B Leclair 1, M A Rudnicki 1, K Jardine 1
PMCID: PMC328987  PMID: 1945853

Abstract

The Pgk-1 gene encodes the housekeeping enzyme, 3-phosphoglycerate kinase, and is ubiquitously expressed. This gene resides on the X chromosome in mammals and is always expressed except where it is silenced along with most other genes on the inactive X chromosome of female somatic cells or male germ cells. The Pgk-1 promoter is in a region rich in nucleotides G and C. This promoter can efficiently drive high levels of expression of reporter genes such as E. coli lacZ and neo. We have determined that the 120 bp upstream of the transcription start site functions as a core promoter. Upstream of this is a 320 bp region which enhances transcription from the core promoter in an orientation and position independent fashion. This 320 bp region does not enhance transcription from the core promoter of the SV40 early region. Nuclear proteins bind to this 320 bp fragment although the restricted regions to which binding can be demonstrated with gel mobility shift assays suggests that the activity of the enhancer may be mediated by factors which bind at multiple sites each with low affinity.

Full text

PDF
5755

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adra C. N., Boer P. H., McBurney M. W. Cloning and expression of the mouse pgk-1 gene and the nucleotide sequence of its promoter. Gene. 1987;60(1):65–74. doi: 10.1016/0378-1119(87)90214-9. [DOI] [PubMed] [Google Scholar]
  2. Bartlett M. H., Adra C. N., Park J., Chapman V. M., McBurney M. W. DNA methylation of two X chromosome genes in female somatic and embryonal carcinoma cells. Somat Cell Mol Genet. 1991 Jan;17(1):35–47. doi: 10.1007/BF01233203. [DOI] [PubMed] [Google Scholar]
  3. Bartlett M. H., Adra C. N., Park J., Chapman V. M., McBurney M. W. DNA methylation of two X chromosome genes in female somatic and embryonal carcinoma cells. Somat Cell Mol Genet. 1991 Jan;17(1):35–47. doi: 10.1007/BF01233203. [DOI] [PubMed] [Google Scholar]
  4. Benezra R., Davis R. L., Lassar A., Tapscott S., Thayer M., Lockshon D., Weintraub H. Id: a negative regulator of helix-loop-helix DNA binding proteins. Control of terminal myogenic differentiation. Ann N Y Acad Sci. 1990;599:1–11. doi: 10.1111/j.1749-6632.1990.tb42359.x. [DOI] [PubMed] [Google Scholar]
  5. Benoist C., Chambon P. In vivo sequence requirements of the SV40 early promotor region. Nature. 1981 Mar 26;290(5804):304–310. doi: 10.1038/290304a0. [DOI] [PubMed] [Google Scholar]
  6. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  7. Boer P. H., Potten H., Adra C. N., Jardine K., Mullhofer G., McBurney M. W. Polymorphisms in the coding and noncoding regions of murine Pgk-1 alleles. Biochem Genet. 1990 Jun;28(5-6):299–308. doi: 10.1007/BF02401419. [DOI] [PubMed] [Google Scholar]
  8. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chodosh L. A., Carthew R. W., Sharp P. A. A single polypeptide possesses the binding and transcription activities of the adenovirus major late transcription factor. Mol Cell Biol. 1986 Dec;6(12):4723–4733. doi: 10.1128/mcb.6.12.4723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Corden J., Wasylyk B., Buchwalder A., Sassone-Corsi P., Kedinger C., Chambon P. Promoter sequences of eukaryotic protein-coding genes. Science. 1980 Sep 19;209(4463):1406–1414. doi: 10.1126/science.6251548. [DOI] [PubMed] [Google Scholar]
  11. Deng T., Li Y., Jolliff K., Johnson L. F. The mouse thymidylate synthase promoter: essential elements are in close proximity to the transcriptional initiation sites. Mol Cell Biol. 1989 Sep;9(9):4079–4082. doi: 10.1128/mcb.9.9.4079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dinsmore J. H., Solomon F. Inhibition of MAP2 expression affects both morphological and cell division phenotypes of neuronal differentiation. Cell. 1991 Feb 22;64(4):817–826. doi: 10.1016/0092-8674(91)90510-6. [DOI] [PubMed] [Google Scholar]
  14. Fried M., Crothers D. M. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. doi: 10.1093/nar/9.23.6505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gartler S. M., Riggs A. D. Mammalian X-chromosome inactivation. Annu Rev Genet. 1983;17:155–190. doi: 10.1146/annurev.ge.17.120183.001103. [DOI] [PubMed] [Google Scholar]
  16. Hawley T. S., Sabourin L. A., Hawley R. G. Comparative analysis of retroviral vector expression in mouse embryonal carcinoma cells. Plasmid. 1989 Sep;22(2):120–131. doi: 10.1016/0147-619x(89)90021-8. [DOI] [PubMed] [Google Scholar]
  17. Jindal H. K., Vishwanatha J. K. Functional identity of a primer recognition protein as phosphoglycerate kinase. J Biol Chem. 1990 Apr 25;265(12):6540–6543. [PubMed] [Google Scholar]
  18. Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
  19. Keith D. H., Singer-Sam J., Riggs A. D. Active X chromosome DNA is unmethylated at eight CCGG sites clustered in a guanine-plus-cytosine-rich island at the 5' end of the gene for phosphoglycerate kinase. Mol Cell Biol. 1986 Nov;6(11):4122–4125. doi: 10.1128/mcb.6.11.4122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kothary R., Clapoff S., Darling S., Perry M. D., Moran L. A., Rossant J. Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice. Development. 1989 Apr;105(4):707–714. doi: 10.1242/dev.105.4.707. [DOI] [PubMed] [Google Scholar]
  21. Lewin B. Commitment and activation at pol II promoters: a tail of protein-protein interactions. Cell. 1990 Jun 29;61(7):1161–1164. doi: 10.1016/0092-8674(90)90675-5. [DOI] [PubMed] [Google Scholar]
  22. Luo X. C., Kim K. H. An enhancer element in the house-keeping promoter for acetyl-CoA carboxylase gene. Nucleic Acids Res. 1990 Jun 11;18(11):3249–3254. doi: 10.1093/nar/18.11.3249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marko M. A., Chipperfield R., Birnboim H. C. A procedure for the large-scale isolation of highly purified plasmid DNA using alkaline extraction and binding to glass powder. Anal Biochem. 1982 Apr;121(2):382–387. doi: 10.1016/0003-2697(82)90497-3. [DOI] [PubMed] [Google Scholar]
  24. McBurney M. W., Adamson E. D. Studies on the activity of the X chromosomes in female teratocarcinoma cells in culture. Cell. 1976 Sep;9(1):57–70. doi: 10.1016/0092-8674(76)90052-0. [DOI] [PubMed] [Google Scholar]
  25. McBurney M. W., Rogers B. J. Isolation of male embryonal carcinoma cells and their chromosome replication patterns. Dev Biol. 1982 Feb;89(2):503–508. doi: 10.1016/0012-1606(82)90338-4. [DOI] [PubMed] [Google Scholar]
  26. McBurney M. W., Strutt B. J. Genetic activity of X chromosomes in pluripotent female teratocarcinoma cells and their differentiated progeny. Cell. 1980 Sep;21(2):357–364. doi: 10.1016/0092-8674(80)90472-9. [DOI] [PubMed] [Google Scholar]
  27. McBurney M. W. X chromosome inactivation: a hypothesis. Bioessays. 1988 Aug-Sep;9(2-3):85–88. doi: 10.1002/bies.950090211. [DOI] [PubMed] [Google Scholar]
  28. Meehan R. R., Lewis J. D., McKay S., Kleiner E. L., Bird A. P. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell. 1989 Aug 11;58(3):499–507. doi: 10.1016/0092-8674(89)90430-3. [DOI] [PubMed] [Google Scholar]
  29. Melton D. W., Konecki D. S., Brennand J., Caskey C. T. Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2147–2151. doi: 10.1073/pnas.81.7.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  31. Norton P. A., Coffin J. M. Bacterial beta-galactosidase as a marker of Rous sarcoma virus gene expression and replication. Mol Cell Biol. 1985 Feb;5(2):281–290. doi: 10.1128/mcb.5.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ogden J. E., Stanway C., Kim S., Mellor J., Kingsman A. J., Kingsman S. M. Efficient expression of the Saccharomyces cerevisiae PGK gene depends on an upstream activation sequence but does not require TATA sequences. Mol Cell Biol. 1986 Dec;6(12):4335–4343. doi: 10.1128/mcb.6.12.4335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Owen T. A., Bortell R., Yocum S. A., Smock S. L., Zhang M., Abate C., Shalhoub V., Aronin N., Wright K. L., van Wijnen A. J. Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9990–9994. doi: 10.1073/pnas.87.24.9990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Park J. H., Taylor M. W. Analysis of signals controlling expression of the Chinese hamster ovary aprt gene. Mol Cell Biol. 1988 Jun;8(6):2536–2544. doi: 10.1128/mcb.8.6.2536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Parkhurst S. M., Bopp D., Ish-Horowicz D. X:A ratio, the primary sex-determining signal in Drosophila, is transduced by helix-loop-helix proteins. Cell. 1990 Dec 21;63(6):1179–1191. doi: 10.1016/0092-8674(90)90414-a. [DOI] [PubMed] [Google Scholar]
  36. Pfeifer G. P., Riggs A. D. Chromatin differences between active and inactive X chromosomes revealed by genomic footprinting of permeabilized cells using DNase I and ligation-mediated PCR. Genes Dev. 1991 Jun;5(6):1102–1113. doi: 10.1101/gad.5.6.1102. [DOI] [PubMed] [Google Scholar]
  37. Pfeifer G. P., Tanguay R. L., Steigerwald S. D., Riggs A. D. In vivo footprint and methylation analysis by PCR-aided genomic sequencing: comparison of active and inactive X chromosomal DNA at the CpG island and promoter of human PGK-1. Genes Dev. 1990 Aug;4(8):1277–1287. doi: 10.1101/gad.4.8.1277. [DOI] [PubMed] [Google Scholar]
  38. Pietrzkowski Z., Alder H., Chang C. D., Ku D. H., Baserga R. Characterization of an enhancer-like structure in the promoter region of the proliferating cell nuclear antigen (PCNA) gene. Exp Cell Res. 1991 Apr;193(2):283–290. doi: 10.1016/0014-4827(91)90098-f. [DOI] [PubMed] [Google Scholar]
  39. Pratt M. A., Kralova J., McBurney M. W. A dominant negative mutation of the alpha retinoic acid receptor gene in a retinoic acid-nonresponsive embryonal carcinoma cell. Mol Cell Biol. 1990 Dec;10(12):6445–6453. doi: 10.1128/mcb.10.12.6445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ptashne M., Gann A. A. Activators and targets. Nature. 1990 Jul 26;346(6282):329–331. doi: 10.1038/346329a0. [DOI] [PubMed] [Google Scholar]
  41. Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
  42. Singer-Sam J., Grant M., LeBon J. M., Okuyama K., Chapman V., Monk M., Riggs A. D. Use of a HpaII-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Mol Cell Biol. 1990 Sep;10(9):4987–4989. doi: 10.1128/mcb.10.9.4987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  44. Séguin C., Felber B. K., Carter A. D., Hamer D. H. Competition for cellular factors that activate metallothionein gene transcription. Nature. 1984 Dec 20;312(5996):781–785. doi: 10.1038/312781a0. [DOI] [PubMed] [Google Scholar]
  45. Tamaru M., Nagao Y., Taira M., Tatibana M., Masamune Y., Nakanishi Y. Selective activation of testis-specific genes in cultured rat spermatogenic cells. Biochim Biophys Acta. 1990 Jul 30;1049(3):331–338. doi: 10.1016/0167-4781(90)90106-c. [DOI] [PubMed] [Google Scholar]
  46. Thomas K. R., Capecchi M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987 Nov 6;51(3):503–512. doi: 10.1016/0092-8674(87)90646-5. [DOI] [PubMed] [Google Scholar]
  47. Torres M., Sánchez L. The scute (T4) gene acts as a numerator element of the X:a signal that determines the state of activity of sex-lethal in Drosophila. EMBO J. 1989 Oct;8(10):3079–3086. doi: 10.1002/j.1460-2075.1989.tb08459.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]
  49. Yenofsky R. L., Fine M., Pellow J. W. A mutant neomycin phosphotransferase II gene reduces the resistance of transformants to antibiotic selection pressure. Proc Natl Acad Sci U S A. 1990 May;87(9):3435–3439. doi: 10.1073/pnas.87.9.3435. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES