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. 1991 Sep;55(3):451–458. doi: 10.1128/mr.55.3.451-458.1991

DNA methylation and gene expression.

A Razin 1, H Cedar 1
PMCID: PMC372829  PMID: 1943996

Abstract

A large body of evidence demonstrates that DNA methylation plays a role in gene regulation in animal cells. Not only is there a correlation between gene transcription and undermethylation, but also transfection experiments clearly show that the presence of methyl moieties inhibits gene expression in vivo. Furthermore, gene activation can be induced by treatment of cells with 5-azacytidine, a potent demethylating agent. Methylation appears to influence gene expression by affecting the interactions with DNA of both chromatin proteins and specific transcription factors. Although methylation patterns are very stable in somatic cells, the early embryo is characterized by large alterations in DNA modification. New methodologies are now becoming available for studying methylation at this stage and in the germ line. During development, tissue-specific genes undergo demethylation in their tissue of expression. In tissue culture cells this process is highly specific and appears to involve an active mechanism which takes place in the absence of DNA replication. The X chromosome undergoes inactivation during development; this is accompanied by de novo methylation, which appears necessary to stably maintain its silent state. As opposed to the programmed changes in DNA methylation which occur in vivo, immortalized tissue culture cells demonstrate alterations in DNA modification which take place over a long time scale and which appear to be the result of selective pressures present during the growth of these cells in culture.

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Selected References

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

  1. Andrulis I. L., Barrett M. T. DNA methylation patterns associated with asparagine synthetase expression in asparagine-overproducing and -auxotrophic cells. Mol Cell Biol. 1989 Jul;9(7):2922–2927. doi: 10.1128/mcb.9.7.2922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antequera F., Boyes J., Bird A. High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell. 1990 Aug 10;62(3):503–514. doi: 10.1016/0092-8674(90)90015-7. [DOI] [PubMed] [Google Scholar]
  3. Becker P. B., Ruppert S., Schütz G. Genomic footprinting reveals cell type-specific DNA binding of ubiquitous factors. Cell. 1987 Nov 6;51(3):435–443. doi: 10.1016/0092-8674(87)90639-8. [DOI] [PubMed] [Google Scholar]
  4. Bednarik D. P., Cook J. A., Pitha P. M. Inactivation of the HIV LTR by DNA CpG methylation: evidence for a role in latency. EMBO J. 1990 Apr;9(4):1157–1164. doi: 10.1002/j.1460-2075.1990.tb08222.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Bestor T., Laudano A., Mattaliano R., Ingram V. Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol. 1988 Oct 20;203(4):971–983. doi: 10.1016/0022-2836(88)90122-2. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Bird A. P. DNA methylation--how important in gene control? Nature. 1984 Feb 9;307(5951):503–504. doi: 10.1038/307503a0. [DOI] [PubMed] [Google Scholar]
  9. Bird A. P. Use of restriction enzymes to study eukaryotic DNA methylation: II. The symmetry of methylated sites supports semi-conservative copying of the methylation pattern. J Mol Biol. 1978 Jan 5;118(1):49–60. doi: 10.1016/0022-2836(78)90243-7. [DOI] [PubMed] [Google Scholar]
  10. Buschhausen G., Wittig B., Graessmann M., Graessmann A. Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1177–1181. doi: 10.1073/pnas.84.5.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Busslinger M., Hurst J., Flavell R. A. DNA methylation and the regulation of globin gene expression. Cell. 1983 Aug;34(1):197–206. doi: 10.1016/0092-8674(83)90150-2. [DOI] [PubMed] [Google Scholar]
  12. Cedar H. DNA methylation and gene activity. Cell. 1988 Apr 8;53(1):3–4. doi: 10.1016/0092-8674(88)90479-5. [DOI] [PubMed] [Google Scholar]
  13. Cedar H., Razin A. DNA methylation and development. Biochim Biophys Acta. 1990 May 24;1049(1):1–8. doi: 10.1016/0167-4781(90)90076-e. [DOI] [PubMed] [Google Scholar]
  14. Cedar H., Solage A., Glaser G., Razin A. Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. Nucleic Acids Res. 1979;6(6):2125–2132. doi: 10.1093/nar/6.6.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  16. Doerfler W., Langner K. D., Knebel D., Weyer U., Dobrzanski P., Knust-Kron B. Site-specific promoter methylations and gene inactivation. Prog Clin Biol Res. 1985;198:133–155. [PubMed] [Google Scholar]
  17. Driscoll D. J., Migeon B. R. Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations. Somat Cell Mol Genet. 1990 May;16(3):267–282. doi: 10.1007/BF01233363. [DOI] [PubMed] [Google Scholar]
  18. Feinberg A. P., Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983 Jan 6;301(5895):89–92. doi: 10.1038/301089a0. [DOI] [PubMed] [Google Scholar]
  19. Fradin A., Manley J. L., Prives C. L. Methylation of simian virus 40 Hpa II site affects late, but not early, viral gene expression. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5142–5146. doi: 10.1073/pnas.79.17.5142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Frank D., Lichtenstein M., Paroush Z., Bergman Y., Shani M., Razin A., Cedar H. Demethylation of genes in animal cells. Philos Trans R Soc Lond B Biol Sci. 1990 Jan 30;326(1235):241–251. doi: 10.1098/rstb.1990.0008. [DOI] [PubMed] [Google Scholar]
  21. Gautsch J. W., Wilson M. C. Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression. Nature. 1983 Jan 6;301(5895):32–37. doi: 10.1038/301032a0. [DOI] [PubMed] [Google Scholar]
  22. Groudine M., Eisenman R., Weintraub H. Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation. Nature. 1981 Jul 23;292(5821):311–317. doi: 10.1038/292311a0. [DOI] [PubMed] [Google Scholar]
  23. Gruenbaum Y., Cedar H., Razin A. Substrate and sequence specificity of a eukaryotic DNA methylase. Nature. 1982 Feb 18;295(5850):620–622. doi: 10.1038/295620a0. [DOI] [PubMed] [Google Scholar]
  24. Gruenbaum Y., Naveh-Many T., Cedar H., Razin A. Sequence specificity of methylation in higher plant DNA. Nature. 1981 Aug 27;292(5826):860–862. doi: 10.1038/292860a0. [DOI] [PubMed] [Google Scholar]
  25. Harris M. Induction of thymidine kinase in enzyme-deficient Chinese hamster cells. Cell. 1982 Jun;29(2):483–492. doi: 10.1016/0092-8674(82)90165-9. [DOI] [PubMed] [Google Scholar]
  26. Holliday R. The inheritance of epigenetic defects. Science. 1987 Oct 9;238(4824):163–170. doi: 10.1126/science.3310230. [DOI] [PubMed] [Google Scholar]
  27. Höller M., Westin G., Jiricny J., Schaffner W. Sp1 transcription factor binds DNA and activates transcription even when the binding site is CpG methylated. Genes Dev. 1988 Sep;2(9):1127–1135. doi: 10.1101/gad.2.9.1127. [DOI] [PubMed] [Google Scholar]
  28. Iguchi-Ariga S. M., Schaffner W. CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev. 1989 May;3(5):612–619. doi: 10.1101/gad.3.5.612. [DOI] [PubMed] [Google Scholar]
  29. Jablonka E., Goitein R., Marcus M., Cedar H. DNA hypomethylation causes an increase in DNase-I sensitivity and an advance in the time of replication of the entire inactive X chromosome. Chromosoma. 1985;93(2):152–156. doi: 10.1007/BF00293162. [DOI] [PubMed] [Google Scholar]
  30. Jones P. A., Taylor S. M. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980 May;20(1):85–93. doi: 10.1016/0092-8674(80)90237-8. [DOI] [PubMed] [Google Scholar]
  31. Jones P. A., Wolkowicz M. J., Rideout W. M., 3rd, Gonzales F. A., Marziasz C. M., Coetzee G. A., Tapscott S. J. De novo methylation of the MyoD1 CpG island during the establishment of immortal cell lines. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6117–6121. doi: 10.1073/pnas.87.16.6117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Jähner D., Stuhlmann H., Stewart C. L., Harbers K., Löhler J., Simon I., Jaenisch R. De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature. 1982 Aug 12;298(5875):623–628. doi: 10.1038/298623a0. [DOI] [PubMed] [Google Scholar]
  33. Kaslow D. C., Migeon B. R. DNA methylation stabilizes X chromosome inactivation in eutherians but not in marsupials: evidence for multistep maintenance of mammalian X dosage compensation. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6210–6214. doi: 10.1073/pnas.84.17.6210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kelley D. E., Pollok B. A., Atchison M. L., Perry R. P. The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated. Mol Cell Biol. 1988 Feb;8(2):930–937. doi: 10.1128/mcb.8.2.930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Keshet I., Lieman-Hurwitz J., Cedar H. DNA methylation affects the formation of active chromatin. Cell. 1986 Feb 28;44(4):535–543. doi: 10.1016/0092-8674(86)90263-1. [DOI] [PubMed] [Google Scholar]
  36. Keshet I., Yisraeli J., Cedar H. Effect of regional DNA methylation on gene expression. Proc Natl Acad Sci U S A. 1985 May;82(9):2560–2564. doi: 10.1073/pnas.82.9.2560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kobayashi H., Ngernprasirtsiri J., Akazawa T. Transcriptional regulation and DNA methylation in plastids during transitional conversion of chloroplasts to chromoplasts. EMBO J. 1990 Feb;9(2):307–313. doi: 10.1002/j.1460-2075.1990.tb08112.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kolsto A. B., Kollias G., Giguere V., Isobe K. I., Prydz H., Grosveld F. The maintenance of methylation-free islands in transgenic mice. Nucleic Acids Res. 1986 Dec 22;14(24):9667–9678. [PMC free article] [PubMed] [Google Scholar]
  39. Konieczny S. F., Emerson C. P., Jr 5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells: evidence for regulatory genes controlling determination. Cell. 1984 Oct;38(3):791–800. doi: 10.1016/0092-8674(84)90274-5. [DOI] [PubMed] [Google Scholar]
  40. Kratzer P. G., Chapman V. M., Lambert H., Evans R. E., Liskay R. M. Differences in the DNA of the inactive X chromosomes of fetal and extraembryonic tissues of mice. Cell. 1983 May;33(1):37–42. doi: 10.1016/0092-8674(83)90332-x. [DOI] [PubMed] [Google Scholar]
  41. Kruczek I., Doerfler W. Expression of the chloramphenicol acetyltransferase gene in mammalian cells under the control of adenovirus type 12 promoters: effect of promoter methylation on gene expression. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7586–7590. doi: 10.1073/pnas.80.24.7586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Kunnath L., Locker J. Developmental changes in the methylation of the rat albumin and alpha-fetoprotein genes. EMBO J. 1983;2(3):317–324. doi: 10.1002/j.1460-2075.1983.tb01425.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lassar A. B., Paterson B. M., Weintraub H. Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell. 1986 Dec 5;47(5):649–656. doi: 10.1016/0092-8674(86)90507-6. [DOI] [PubMed] [Google Scholar]
  44. Liskay R. M., Evans R. J. Inactive X chromosome DNA does not function in DNA-mediated cell transformation for the hypoxanthine phosphoribosyltransferase gene. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4895–4898. doi: 10.1073/pnas.77.8.4895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Lock L. F., Takagi N., Martin G. R. Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation. Cell. 1987 Jan 16;48(1):39–46. doi: 10.1016/0092-8674(87)90353-9. [DOI] [PubMed] [Google Scholar]
  46. Mann V., Szyf M., Razin A., Chriqui-Zeira E., Kedar E. Characterization of a tumorigenic murine T-lymphoid-cell line spontaneously derived from an IL-2-dependent T-cell line. Int J Cancer. 1986 May 15;37(5):781–786. doi: 10.1002/ijc.2910370521. [DOI] [PubMed] [Google Scholar]
  47. McGhee J. D., Ginder G. D. Specific DNA methylation sites in the vicinity of the chicken beta-globin genes. Nature. 1979 Aug 2;280(5721):419–420. doi: 10.1038/280419a0. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. Mohandas T., Sparkes R. S., Shapiro L. J. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science. 1981 Jan 23;211(4480):393–396. doi: 10.1126/science.6164095. [DOI] [PubMed] [Google Scholar]
  50. Monk M., Boubelik M., Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987 Mar;99(3):371–382. doi: 10.1242/dev.99.3.371. [DOI] [PubMed] [Google Scholar]
  51. Nelson K. J., Mather E. L., Perry R. P. Lipopolysaccharide-induced transcription of the kappa immunoglobulin locus occurs on both alleles and is independent of methylation status. Nucleic Acids Res. 1984 Feb 24;12(4):1911–1923. doi: 10.1093/nar/12.4.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Oshima R. G., Trevor K., Shevinsky L. H., Ryder O. A., Ceceña G. Identification of the gene coding for the Endo B murine cytokeratin and its methylated, stable inactive state in mouse nonepithelial cells. Genes Dev. 1988 May;2(5):505–516. doi: 10.1101/gad.2.5.505. [DOI] [PubMed] [Google Scholar]
  53. Otto S. P., Walbot V. DNA methylation in eukaryotes: kinetics of demethylation and de novo methylation during the life cycle. Genetics. 1990 Feb;124(2):429–437. doi: 10.1093/genetics/124.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Paroush Z., Keshet I., Yisraeli J., Cedar H. Dynamics of demethylation and activation of the alpha-actin gene in myoblasts. Cell. 1990 Dec 21;63(6):1229–1237. doi: 10.1016/0092-8674(90)90418-e. [DOI] [PubMed] [Google Scholar]
  55. Paterno G. D., Adra C. N., McBurney M. W. X chromosome reactivation in mouse embryonal carcinoma cells. Mol Cell Biol. 1985 Oct;5(10):2705–2712. doi: 10.1128/mcb.5.10.2705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Pfeifer G. P., Steigerwald S. D., Hansen R. S., Gartler S. M., Riggs A. D. Polymerase chain reaction-aided genomic sequencing of an X chromosome-linked CpG island: methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8252–8256. doi: 10.1073/pnas.87.21.8252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. 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]
  58. Pollack Y., Stein R., Razin A., Cedar H. Methylation of foreign DNA sequences in eukaryotic cells. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6463–6467. doi: 10.1073/pnas.77.11.6463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Razin A., Feldmesser E., Kafri T., Szyf M. Cell specific DNA methylation patterns; formation and a nucleosome locking model for their function. Prog Clin Biol Res. 1985;198:239–253. [PubMed] [Google Scholar]
  60. Razin A., Riggs A. D. DNA methylation and gene function. Science. 1980 Nov 7;210(4470):604–610. doi: 10.1126/science.6254144. [DOI] [PubMed] [Google Scholar]
  61. Razin A., Szyf M., Kafri T., Roll M., Giloh H., Scarpa S., Carotti D., Cantoni G. L. Replacement of 5-methylcytosine by cytosine: a possible mechanism for transient DNA demethylation during differentiation. Proc Natl Acad Sci U S A. 1986 May;83(9):2827–2831. doi: 10.1073/pnas.83.9.2827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Riggs A. D., Jones P. A. 5-methylcytosine, gene regulation, and cancer. Adv Cancer Res. 1983;40:1–30. doi: 10.1016/s0065-230x(08)60678-8. [DOI] [PubMed] [Google Scholar]
  63. Saluz H. P., Jiricny J., Jost J. P. Genomic sequencing reveals a positive correlation between the kinetics of strand-specific DNA demethylation of the overlapping estradiol/glucocorticoid-receptor binding sites and the rate of avian vitellogenin mRNA synthesis. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7167–7171. doi: 10.1073/pnas.83.19.7167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Sanford J. P., Clark H. J., Chapman V. M., Rossant J. Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse. Genes Dev. 1987 Dec;1(10):1039–1046. doi: 10.1101/gad.1.10.1039. [DOI] [PubMed] [Google Scholar]
  65. Schorderet D. F., Keitges E. A., Dubois P. M., Gartler S. M. Inactivation and reactivation of sex-linked steroid sulfatase gene in murine cell culture. Somat Cell Mol Genet. 1988 Mar;14(2):113–121. doi: 10.1007/BF01534396. [DOI] [PubMed] [Google Scholar]
  66. Selig S., Ariel M., Goitein R., Marcus M., Cedar H. Regulation of mouse satellite DNA replication time. EMBO J. 1988 Feb;7(2):419–426. doi: 10.1002/j.1460-2075.1988.tb02829.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Shemer R., Walsh A., Eisenberg S., Breslow J. L., Razin A. Tissue-specific methylation patterns and expression of the human apolipoprotein AI gene. J Biol Chem. 1990 Jan 15;265(2):1010–1015. [PubMed] [Google Scholar]
  68. 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]
  69. Singer J., Roberts-Ems J., Luthardt F. W., Riggs A. D. Methylation of DNA in mouse early embryos, teratocarcinoma cells and adult tissues of mouse and rabbit. Nucleic Acids Res. 1979 Dec 20;7(8):2369–2385. doi: 10.1093/nar/7.8.2369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Stein R., Gruenbaum Y., Pollack Y., Razin A., Cedar H. Clonal inheritance of the pattern of DNA methylation in mouse cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):61–65. doi: 10.1073/pnas.79.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Stein R., Sciaky-Gallili N., Razin A., Cedar H. Pattern of methylation of two genes coding for housekeeping functions. Proc Natl Acad Sci U S A. 1983 May;80(9):2422–2426. doi: 10.1073/pnas.80.9.2422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Stuhlmann H., Jähner D., Jaenisch R. Infectivity and methylation of retroviral genomes is correlated with expression in the animal. Cell. 1981 Oct;26(2 Pt 2):221–232. doi: 10.1016/0092-8674(81)90305-6. [DOI] [PubMed] [Google Scholar]
  73. Szyf M., Eliasson L., Mann V., Klein G., Razin A. Cellular and viral DNA hypomethylation associated with induction of Epstein-Barr virus lytic cycle. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8090–8094. doi: 10.1073/pnas.82.23.8090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Szyf M., Tanigawa G., McCarthy P. L., Jr A DNA signal from the Thy-1 gene defines de novo methylation patterns in embryonic stem cells. Mol Cell Biol. 1990 Aug;10(8):4396–4400. doi: 10.1128/mcb.10.8.4396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Taylor S. M., Jones P. A. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell. 1979 Aug;17(4):771–779. doi: 10.1016/0092-8674(79)90317-9. [DOI] [PubMed] [Google Scholar]
  76. Thompson J. P., Granoff A., Willis D. B. Trans-activation of a methylated adenovirus promoter by a frog virus 3 protein. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7688–7692. doi: 10.1073/pnas.83.20.7688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Toth M., Lichtenberg U., Doerfler W. Genomic sequencing reveals a 5-methylcytosine-free domain in active promoters and the spreading of preimposed methylation patterns. Proc Natl Acad Sci U S A. 1989 May;86(10):3728–3732. doi: 10.1073/pnas.86.10.3728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Vardimon L., Kressmann A., Cedar H., Maechler M., Doerfler W. Expression of a cloned adenovirus gene is inhibited by in vitro methylation. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1073–1077. doi: 10.1073/pnas.79.4.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Venolia L., Gartler S. M., Wassman E. R., Yen P., Mohandas T., Shapiro L. J. Transformation with DNA from 5-azacytidine-reactivated X chromosomes. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2352–2354. doi: 10.1073/pnas.79.7.2352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Waalwijk C., Flavell R. A. MspI, an isoschizomer of hpaII which cleaves both unmethylated and methylated hpaII sites. Nucleic Acids Res. 1978 Sep;5(9):3231–3236. doi: 10.1093/nar/5.9.3231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Watt F., Molloy P. L. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev. 1988 Sep;2(9):1136–1143. doi: 10.1101/gad.2.9.1136. [DOI] [PubMed] [Google Scholar]
  82. Weisshaar B., Langner K. D., Jüttermann R., Müller U., Zock C., Klimkait T., Doerfler W. Reactivation of the methylation-inactivated late E2A promoter of adenovirus type 2 by E1A (13 S) functions. J Mol Biol. 1988 Jul 20;202(2):255–270. doi: 10.1016/0022-2836(88)90456-1. [DOI] [PubMed] [Google Scholar]
  83. Wiebauer K., Jiricny J. In vitro correction of G.T mispairs to G.C pairs in nuclear extracts from human cells. Nature. 1989 May 18;339(6221):234–236. doi: 10.1038/339234a0. [DOI] [PubMed] [Google Scholar]
  84. Wigler M., Levy D., Perucho M. The somatic replication of DNA methylation. Cell. 1981 Apr;24(1):33–40. doi: 10.1016/0092-8674(81)90498-0. [DOI] [PubMed] [Google Scholar]
  85. Wilson V. L., Jones P. A. DNA methylation decreases in aging but not in immortal cells. Science. 1983 Jun 3;220(4601):1055–1057. doi: 10.1126/science.6844925. [DOI] [PubMed] [Google Scholar]
  86. Wise T. L., Harris M. Deletion and hypermethylation of thymidine kinase gene in V79 Chinese hamster cells resistant to bromodeoxyuridine. Somat Cell Mol Genet. 1988 Nov;14(6):567–581. doi: 10.1007/BF01535311. [DOI] [PubMed] [Google Scholar]
  87. Wolf S. F., Migeon B. R. Studies of X chromosome DNA methylation in normal human cells. Nature. 1982 Feb 25;295(5851):667–671. doi: 10.1038/295667a0. [DOI] [PubMed] [Google Scholar]
  88. Yisraeli J., Adelstein R. S., Melloul D., Nudel U., Yaffe D., Cedar H. Muscle-specific activation of a methylated chimeric actin gene. Cell. 1986 Aug 1;46(3):409–416. doi: 10.1016/0092-8674(86)90661-6. [DOI] [PubMed] [Google Scholar]
  89. Yisraeli J., Frank D., Razin A., Cedar H. Effect of in vitro DNA methylation on beta-globin gene expression. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4638–4642. doi: 10.1073/pnas.85.13.4638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. van der Ploeg L. H., Flavell R. A. DNA methylation in the human gamma delta beta-globin locus in erythroid and nonerythroid tissues. Cell. 1980 Apr;19(4):947–958. doi: 10.1016/0092-8674(80)90086-0. [DOI] [PubMed] [Google Scholar]

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