Abstract
The sensitivity to DNase I digestion of the gene encoding rat phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) was assessed during development and prior to the onset of expression. This gene is resistant to DNase I digestion in nuclei isolated from livers of 19-day rat fetuses. Gradual acquisition of sensitivity of the phosphoenolpyruvate carboxykinase gene, which starts later than the 19th day of gestation and is completed by the 21st day, occurs before initiation of gene expression. As transcription of the phosphoenolpyruvate carboxykinase gene is not detected until birth, the events observed may represent a shift from a dormant to an active gene. Injection of N6,O2-dibutyryladenosine 3',5'-cyclic monophosphate into fetuses on the 19th day of gestation induces gene expression and sensitivity to DNase I digestion within 3 hr of treatment. While this short treatment does not affect the methylation pattern of the gene, longer treatment of fetuses (2 days) with dibutyryl-cAMP results in premature hypomethylation of the gene. A hierarchy of modifications of the phosphoenolpyruvate carboxykinase gene during development is discussed.
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- Ballard F. J., Hanson R. W. Phosphoenolpyruvate carboxykinase and pyruvate carboxylase in developing rat liver. Biochem J. 1967 Sep;104(3):866–871. doi: 10.1042/bj1040866. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Becker P., Renkawitz R., Schütz G. Tissue-specific DNaseI hypersensitive sites in the 5'-flanking sequences of the tryptophan oxygenase and the tyrosine aminotransferase genes. EMBO J. 1984 Sep;3(9):2015–2020. doi: 10.1002/j.1460-2075.1984.tb02084.x. [DOI] [PMC free article] [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., Szyf M., Mencher D., Razin A., Reshef L. Tissue-specific hypomethylation and expression of rat phosphoenolpyruvate carboxykinase gene induced by in vivo treatment of fetuses and neonates with 5-azacytidine. Biochemistry. 1985 Sep 10;24(19):5015–5019. doi: 10.1021/bi00340a009. [DOI] [PubMed] [Google Scholar]
- Burch J. B., Weintraub H. Temporal order of chromatin structural changes associated with activation of the major chicken vitellogenin gene. Cell. 1983 May;33(1):65–76. doi: 10.1016/0092-8674(83)90335-5. [DOI] [PubMed] [Google Scholar]
- Cimbala M. A., Lamers W. H., Nelson K., Monahan J. E., Yoo-Warren H., Hanson R. W. Rapid changes in the concentration of phosphoenolpyruvate carboxykinase mRNA in rat liver and kidney. Effects of insulin and cyclic AMP. J Biol Chem. 1982 Jul 10;257(13):7629–7636. [PubMed] [Google Scholar]
- Elgin S. C. DNAase I-hypersensitive sites of chromatin. Cell. 1981 Dec;27(3 Pt 2):413–415. doi: 10.1016/0092-8674(81)90381-0. [DOI] [PubMed] [Google Scholar]
- Fritton H. P., Igo-Kemenes T., Nowock J., Strech-Jurk U., Theisen M., Sippel A. E. Alternative sets of DNase I-hypersensitive sites characterize the various functional states of the chicken lysozyme gene. Nature. 1984 Sep 13;311(5982):163–165. doi: 10.1038/311163a0. [DOI] [PubMed] [Google Scholar]
- Garel A., Axel R. Selective digestion of transcriptionally active ovalbumin genes from oviduct nuclei. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3966–3970. doi: 10.1073/pnas.73.11.3966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Girard J. R., Kervran A., Soufflet E., Assan R. Factors affecting the secretion of insulin and glucagon by the rat fetus. Diabetes. 1974 Apr;23(4):310–317. doi: 10.2337/diab.23.4.310. [DOI] [PubMed] [Google Scholar]
- Greengard O., Federman M., Knox W. E. Cytomorphometry of developing rat liver and its application to enzymic differentiation. J Cell Biol. 1972 Feb;52(2):261–272. doi: 10.1083/jcb.52.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groudine M., Weintraub H. Activation of globin genes during chicken development. Cell. 1981 May;24(2):393–401. doi: 10.1016/0092-8674(81)90329-9. [DOI] [PubMed] [Google Scholar]
- Hanson R. W., Fisher L., Ballard F. J., Reshef L. The regulation of phosphoenolpyruvate carboxykinase in fetal rat liver. Enzyme. 1973;15(1):97–110. [PubMed] [Google Scholar]
- Hewish D. R., Burgoyne L. A. Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease. Biochem Biophys Res Commun. 1973 May 15;52(2):504–510. doi: 10.1016/0006-291x(73)90740-7. [DOI] [PubMed] [Google Scholar]
- Kioussis D., Hamilton R., Hanson R. W., Tilghman S. M., Taylor J. M. Construction and cloning of rat albumin structural gene sequences. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4370–4374. doi: 10.1073/pnas.76.9.4370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamers W. H., Hanson R. W., Meisner H. M. cAMP stimulates transcription of the gene for cytosolic phosphoenolpyruvate carboxykinase in rat liver nuclei. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5137–5141. doi: 10.1073/pnas.79.17.5137. [DOI] [PMC free article] [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., Cohen H., Benvenisty N., Meyuhas O., Reshef L. Primary activation of cytosolic phosphoenolpyruvate carboxykinase gene in fetal rat liver and the biogenesis of its mRNA. Eur J Biochem. 1984 May 15;141(1):199–203. doi: 10.1111/j.1432-1033.1984.tb08175.x. [DOI] [PubMed] [Google Scholar]
- Mencher D., Shouval D., Reshef L. Premature appearance of hepatic phosphoenolpyruvate carboxykinase in fetal rats, not mediated by adenosine 3':5'-monophosphate. Eur J Biochem. 1979 Dec 17;102(2):489–495. doi: 10.1111/j.1432-1033.1979.tb04264.x. [DOI] [PubMed] [Google Scholar]
- Nahon J. L., Gal A., Erdos T., Sala-Trepat J. M. Differential DNase I sensitivity of the albumin and alpha-fetoprotein genes in chromatin from rat tissues and cell lines. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5031–5035. doi: 10.1073/pnas.81.16.5031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Razin A., Cedar H. DNA methylation in eukaryotic cells. Int Rev Cytol. 1984;92:159–185. doi: 10.1016/s0074-7696(08)61327-3. [DOI] [PubMed] [Google Scholar]
- Sargent T. D., Jagodzinski L. L., Yang M., Bonner J. Fine structure and evolution of the rat serum albumin gene. Mol Cell Biol. 1981 Oct;1(10):871–883. doi: 10.1128/mcb.1.10.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Senear A. W., Palmiter R. D. Expression of the mouse metallothionein-I gene alters the nuclease hypersensitivity of its 5' regulatory region. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 1):539–547. doi: 10.1101/sqb.1983.047.01.063. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Vedel M., Gomez-Garcia M., Sala M., Sala-Trepat J. M. Changes in methylation pattern of albumin and alpha-fetoprotein genes in developing rat liver and neoplasia. Nucleic Acids Res. 1983 Jul 11;11(13):4335–4354. doi: 10.1093/nar/11.13.4335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinstock R., Sweet R., Weiss M., Cedar H., Axel R. Intragenic DNA spacers interrupt the ovalbumin gene. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1299–1303. doi: 10.1073/pnas.75.3.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weintraub H., Groudine M. Chromosomal subunits in active genes have an altered conformation. Science. 1976 Sep 3;193(4256):848–856. doi: 10.1126/science.948749. [DOI] [PubMed] [Google Scholar]
- Weintraub H., Larsen A., Groudine M. Alpha-Globin-gene switching during the development of chicken embryos: expression and chromosome structure. Cell. 1981 May;24(2):333–344. doi: 10.1016/0092-8674(81)90323-8. [DOI] [PubMed] [Google Scholar]
- Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]
- Wynshaw-Boris A., Lugo T. G., Short J. M., Fournier R. E., Hanson R. W. Identification of a cAMP regulatory region in the gene for rat cytosolic phosphoenolpyruvate carboxykinase (GTP). Use of chimeric genes transfected into hepatoma cells. J Biol Chem. 1984 Oct 10;259(19):12161–12169. [PubMed] [Google Scholar]
- Yeung D., Oliver I. T. Induction of phosphopyruvate carboxylase in neonatal rat liver by adenosine 3',5'-cyclic monophosphate. Biochemistry. 1968 Sep;7(9):3231–3239. doi: 10.1021/bi00849a028. [DOI] [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]
- Zaret K. S., Yamamoto K. R. Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element. Cell. 1984 Aug;38(1):29–38. doi: 10.1016/0092-8674(84)90523-3. [DOI] [PubMed] [Google Scholar]