Abstract
The selective expression of a unique copy gene in several mammalian tissues has been approached by studying the regulatory sequences needed to control expression of the rat phosphoenolpyruvate carboxykinase (PEPCK) gene in transgenic mice. A transgene containing the entire PEPCK gene, including 2.2 kb of the 5'-flanking region and 0.5 kb of the 3'-flanking region, exhibits tissue-specific expression in the liver, kidney, and adipose tissue, as well as the hormonal and developmental regulation inherent to endogenous gene expression. Deletions of the 5'-flanking region of the gene have shown the need for sequences downstream of position -540 of the PEPCK gene for expression in the liver and sequences downstream of position -362 for expression in the kidney. Additional sequences upstream of position -540 (up to -2200) are required for expression in adipose tissue. In addition, the region containing the glucocorticoid-responsive elements of the gene used by the kidney was identified. This same sequence was found to be needed specifically for developmental regulation of gene expression in the kidney and, together with upstream sequences, in the intestine. The apparently distinct sequence requirements in the various tissues indicate that the tissues use different mechanisms for expression of the same gene.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Atchison M. L., Perry R. P. The role of the kappa enhancer and its binding factor NF-kappa B in the developmental regulation of kappa gene transcription. Cell. 1987 Jan 16;48(1):121–128. doi: 10.1016/0092-8674(87)90362-x. [DOI] [PubMed] [Google Scholar]
- Bartke A., Steger R. W., Hodges S. L., Parkening T. A., Collins T. J., Yun J. S., Wagner T. E. Infertility in transgenic female mice with human growth hormone expression: evidence for luteal failure. J Exp Zool. 1988 Oct;248(1):121–124. doi: 10.1002/jez.1402480116. [DOI] [PubMed] [Google Scholar]
- Beale E. G., Chrapkiewicz N. B., Scoble H. A., Metz R. J., Quick D. P., Noble R. L., Donelson J. E., Biemann K., Granner D. K. Rat hepatic cytosolic phosphoenolpyruvate carboxykinase (GTP). Structures of the protein, messenger RNA, and gene. J Biol Chem. 1985 Sep 5;260(19):10748–10760. [PubMed] [Google Scholar]
- Benvenisty N., Mencher D., Meyuhas O., Razin A., Reshef L. Sequential changes in DNA methylation patterns of the rat phosphoenolpyruvate carboxykinase gene during development. Proc Natl Acad Sci U S A. 1985 Jan;82(2):267–271. doi: 10.1073/pnas.82.2.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benvenisty N., Nechushtan H., Cohen H., Reshef L. Separate cis-regulatory elements confer expression of phosphoenolpyruvate carboxykinase (GTP) gene in different cell lines. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1118–1122. doi: 10.1073/pnas.86.4.1118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Cohen H., Gidoni B., Shouval D., Benvenisty N., Mencher D., Meyuhas O., Reshef L. Conservation from rat to human of cytosolic phosphoenolpyruvate carboxykinase and the control of its gene expression. FEBS Lett. 1985 Jan 28;180(2):175–180. doi: 10.1016/0014-5793(85)81066-8. [DOI] [PubMed] [Google Scholar]
- Cook J. S., Weldon S. L., Garcia-Ruiz J. P., Hod Y., Hanson R. W. Nucleotide sequence of the mRNA encoding the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the chicken. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7583–7587. doi: 10.1073/pnas.83.20.7583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doi T., Striker L. J., Quaife C., Conti F. G., Palmiter R., Behringer R., Brinster R., Striker G. E. Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor-1. Am J Pathol. 1988 Jun;131(3):398–403. [PMC free article] [PubMed] [Google Scholar]
- Gordon J. W., Ruddle F. H. Integration and stable germ line transmission of genes injected into mouse pronuclei. Science. 1981 Dec 11;214(4526):1244–1246. doi: 10.1126/science.6272397. [DOI] [PubMed] [Google Scholar]
- Graves R. A., Tontonoz P., Ross S. R., Spiegelman B. M. Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor. Genes Dev. 1991 Mar;5(3):428–437. doi: 10.1101/gad.5.3.428. [DOI] [PubMed] [Google Scholar]
- Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
- Hammer R. E., Krumlauf R., Camper S. A., Brinster R. L., Tilghman S. M. Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. Science. 1987 Jan 2;235(4784):53–58. doi: 10.1126/science.2432657. [DOI] [PubMed] [Google Scholar]
- Hod Y., Cook J. S., Weldon S. L., Short J. M., Wynshaw-Boris A., Hanson R. W. Differential expression of the genes for the mitochondrial and cytosolic forms of phosphoenolpyruvate carboxykinase. Ann N Y Acad Sci. 1986;478:31–45. doi: 10.1111/j.1749-6632.1986.tb15519.x. [DOI] [PubMed] [Google Scholar]
- Hod Y., Morris S. M., Hanson R. W. Induction by cAMP of the mRNA encoding the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the chicken. Identification and characterization of a cDNA clone for the enzyme. J Biol Chem. 1984 Dec 25;259(24):15603–15608. [PubMed] [Google Scholar]
- Imai E., Stromstedt P. E., Quinn P. G., Carlstedt-Duke J., Gustafsson J. A., Granner D. K. Characterization of a complex glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1990 Sep;10(9):4712–4719. doi: 10.1128/mcb.10.9.4712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin A., Chan Y. L., McNally J., Peleg D., Meyuhas O., Wool I. G. The primary structure of rat ribosomal protein L7. The presence near the amino terminus of L7 of five tandem repeats of a sequence of 12 amino acids. J Biol Chem. 1987 Sep 15;262(26):12665–12671. [PubMed] [Google Scholar]
- McGrane M. M., Yun J. S., Moorman A. F., Lamers W. H., Hendrick G. K., Arafah B. M., Park E. A., Wagner T. E., Hanson R. W. Metabolic effects of developmental, tissue-, and cell-specific expression of a chimeric phosphoenolpyruvate carboxykinase (GTP)/bovine growth hormone gene in transgenic mice. J Biol Chem. 1990 Dec 25;265(36):22371–22379. [PubMed] [Google Scholar]
- Meisner H., Loose D. S., Hanson R. W. Effect of hormones on transcription of the gene for cytosolic phosphoenolpyruvate carboxykinase (GTP) in rat kidney. Biochemistry. 1985 Jan 15;24(2):421–425. doi: 10.1021/bi00323a027. [DOI] [PubMed] [Google Scholar]
- Mencher D., Reshef L. Effect of triamcinolone on renal and hepatic phosphoenolpyruvate carboxykinase in the newborn rat. Changes in the rate of synthesis of the enzyme and in the activity of its translatable messenger RNA. Eur J Biochem. 1979 Mar;94(2):581–589. doi: 10.1111/j.1432-1033.1979.tb12928.x. [DOI] [PubMed] [Google Scholar]
- Mendel D. B., Crabtree G. R. HNF-1, a member of a novel class of dimerizing homeodomain proteins. J Biol Chem. 1991 Jan 15;266(2):677–680. [PubMed] [Google Scholar]
- Meyuhas O., Thompson E. A., Jr, Perry R. P. Glucocorticoids selectively inhibit translation of ribosomal protein mRNAs in P1798 lymphosarcoma cells. Mol Cell Biol. 1987 Aug;7(8):2691–2699. doi: 10.1128/mcb.7.8.2691. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minty A. J., Caravatti M., Robert B., Cohen A., Daubas P., Weydert A., Gros F., Buckingham M. E. Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. J Biol Chem. 1981 Jan 25;256(2):1008–1014. [PubMed] [Google Scholar]
- Nechushtan H., Benvenisty N., Brandeis R., Reshef L. Glucocorticoids control phosphoenolpyruvate carboxykinase gene expression in a tissue specific manner. Nucleic Acids Res. 1987 Aug 25;15(16):6405–6417. doi: 10.1093/nar/15.16.6405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park E. A., Roesler W. J., Liu J., Klemm D. J., Gurney A. L., Thatcher J. D., Shuman J., Friedman A., Hanson R. W. The role of the CCAAT/enhancer-binding protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP). Mol Cell Biol. 1990 Dec;10(12):6264–6272. doi: 10.1128/mcb.10.12.6264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pursel V. G., Pinkert C. A., Miller K. F., Bolt D. J., Campbell R. G., Palmiter R. D., Brinster R. L., Hammer R. E. Genetic engineering of livestock. Science. 1989 Jun 16;244(4910):1281–1288. doi: 10.1126/science.2499927. [DOI] [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Roesler W. J., Vandenbark G. R., Hanson R. W. Identification of multiple protein binding domains in the promoter-regulatory region of the phosphoenolpyruvate carboxykinase (GTP) gene. J Biol Chem. 1989 Jun 5;264(16):9657–9664. [PubMed] [Google Scholar]
- Sasaki K., Cripe T. P., Koch S. R., Andreone T. L., Petersen D. D., Beale E. G., Granner D. K. Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin. J Biol Chem. 1984 Dec 25;259(24):15242–15251. [PubMed] [Google Scholar]
- Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986 Sep 26;46(7):963–972. doi: 10.1016/0092-8674(86)90695-1. [DOI] [PubMed] [Google Scholar]
- Shani M. Tissue-specific expression of rat myosin light-chain 2 gene in transgenic mice. Nature. 1985 Mar 21;314(6008):283–286. doi: 10.1038/314283a0. [DOI] [PubMed] [Google Scholar]
- Shoshani T., Benvenisty N., Trus M., Reshef L. Cis-regulatory elements that confer differential expression upon the rat gene encoding phosphoenolpyruvate carboxykinase in kidney and liver. Gene. 1991 May 30;101(2):279–283. doi: 10.1016/0378-1119(91)90424-a. [DOI] [PubMed] [Google Scholar]
- Trus M., Benvenisty N., Cohen H., Reshef L. Developmentally regulated interactions of liver nuclear factors with the rat phosphoenolpyruvate carboxykinase promoter. Mol Cell Biol. 1990 May;10(5):2418–2422. doi: 10.1128/mcb.10.5.2418. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoo-Warren H., Monahan J. E., Short J., Short H., Bruzel A., Wynshaw-Boris A., Meisner H. M., Samols D., Hanson R. W. Isolation and characterization of the gene coding for cytosolic phosphoenolpyruvate carboxykinase (GTP) from the rat. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3656–3660. doi: 10.1073/pnas.80.12.3656. [DOI] [PMC free article] [PubMed] [Google Scholar]