Complexities in Gene Regulation by Promoter Methylation

  • Walter Doerfler
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 3)


The regulation of eukaryotic gene expression presents a multi-faceted problem. It is not limited to the extreme stages of a gene being turned on or switched off. Regulation of gene expression also implies the facility of gene activity to be modulated to various degrees and of promoters to be capable of responding to a variety of internal and environmental stimuli. These stringent requirements can be met by promoter sequences in that they exhibit genetic signals which can be recognized by a considerable number of cellular regulatory proteins. Such promoter signals being vacant or occupied by a specific protein or several proteins confer a certain state of activity upon the promoter and the gene it controls. A multitude of cellular proteins and of promoter signals appear to be involved in the regulation of gene activity. Regulatory significance is not restricted to DNA-protein interactions. Proteinprotein binding may be as important in that promoter-binding proteins might acquire the promoter-congruent conformation by a previous interaction with other proteins. Alternatively, reaching this conformation could be prohibited by linkage to yet other proteins thus obstructing the essential DNA-protein interaction.


Promoter Methylation Methylation Pattern Globin Gene Xenopus Laevis Oocyte Adenovirus Type 
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  1. Baker CC, Ziff EB (1981) Promoters and heterogeneous 5’ termini of the messenger RNAs of adenovirus serotype 2. J Mol Biol 149: 189–221PubMedCrossRefGoogle Scholar
  2. Bennetzen JL (1987) Covalent DNA modification and the regulation of Mutator element transposition in maize. Mol Gen Genet 208: 45–51CrossRefGoogle Scholar
  3. Berk AJ, Lee F, Harrison T, Williams J, Sharp PA (1979) Pre-early adenovirus 5 gene product regulates synthesis of early viral messenger RNAs. Cell 17: 935–944PubMedCrossRefGoogle Scholar
  4. Bestor TH, Ingram VM (1983) Two DNA methyltransferases from murine erythroleukemia cells: Purification, sequence specificity, and mode of interaction with DNA. Proc Natl Acad Sci USA 80: 5559–5563Google Scholar
  5. Bestor T, Laudano A, Mattaliano R, Ingram V (1988) Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxy-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol 203: 971–983PubMedCrossRefGoogle Scholar
  6. Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8: 1499–1504PubMedCrossRefGoogle Scholar
  7. Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321: 209–213PubMedCrossRefGoogle Scholar
  8. Bolden, AH, Ward C, Siedlecki JA, Weissbach A (1984) DNA methylation. Inhibition of de novo and maintenance methylation in vitro by RNA and synthetic polynucleotides. J Biol Chem 259: 12437–12443PubMedGoogle Scholar
  9. Cook JL, Lewis AM Jr (1979) Host response to adenovirus 2-transformed hamster embryo cells. Cancer Res 39: 1455–1461PubMedGoogle Scholar
  10. Boshart M, Weber F, Jahn G, Dorsch-Häsler K, Fleckenstein B, Schaffner W (1985) Avery strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell 41: 521–530PubMedCrossRefGoogle Scholar
  11. Busslinger M, Hurst J, Flavell RA (1983) DNA methylation and the regulation of globin gene expression. Cell 34: 197–206PubMedCrossRefGoogle Scholar
  12. Chandler VL, Walbot V (1986) DNA modification of a maize transposable element correlates with loss of activity. Proc Natl Acad Sci USA 83: 1767–1771PubMedCrossRefGoogle Scholar
  13. Chomet PS, Wessler S, Dellaporta SL (1987) Inactivation of the maize transposable element Activator (Ac) is associated with its DNA modification. EMBO J 6: 295: 302Google Scholar
  14. Church GM, Gilbert W (1984) Genomic sequencing. Proc Nati Acad Sci USA 81: 1991–1995CrossRefGoogle Scholar
  15. Constantinides PG, Jones PA, Gevers W (1977) Functional striated muscle cells from non-myoblast precursors following 5-azacytidine treatment. Nature 267: 364–366PubMedCrossRefGoogle Scholar
  16. Cook JL, Lewis AM Jr (1979) Host response to adenovirus 2-transformed hamster embryo cells. Cancer Res 39: 1455–1461PubMedGoogle Scholar
  17. Cooper DN (1983) Eukaryotic DNA methylation. Hum Genet 64: 315–333PubMedCrossRefGoogle Scholar
  18. Coulondre C, Miller JH, Farabough PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274: 775–780PubMedCrossRefGoogle Scholar
  19. Deumling B (1981) Sequence arrangement of a highly methylated satellite DNA of a plant, Scilla: A tandemly repeated inverted repeat. Proc Natl Acad Sci USA 78: 338–342PubMedCrossRefGoogle Scholar
  20. Dobrzanski P, Hoeveler A, Doerfler W (1988) Inactivation by sequence-specific methylations of adenovims promoters in a cell-free transcription system. J Virol 62: 3941–3946PubMedGoogle Scholar
  21. Doerfler W (1968) The fate of the DNA of adenovirus type 12 in baby hamster kidney cells. Proc Nati Acad Sci USA, 60: 636–643CrossRefGoogle Scholar
  22. Doerfler W (1969) Nonproductive infection of baby hamster kidney cells (BHK21) with adenovirus type 12. Virology 38: 587–606PubMedCrossRefGoogle Scholar
  23. Doerfler W (1981) DNA methylation–A regulatory signal in eukaryotic gene expression. J Gen Virol 57: 1–20PubMedCrossRefGoogle Scholar
  24. Doerfler W (1983) DNA methylation and gene activity. Annu Rev Biochem 52: 93–124PubMedCrossRefGoogle Scholar
  25. Doerfler W (1984a) DNA methylation: role in viral transformation and persistence. In: Klein G (ed) Advances in Viral Oncology, vol 4. Raven, New York, pp 217–247Google Scholar
  26. Doerfler W (1984b) DNA methylation and its functional significance: studies on the adenovirus system. Curr Top Microbiol Immunol 108: 79–98PubMedCrossRefGoogle Scholar
  27. Doerfler W, Kmczek I, Eick D, Vardimon L, Kron B (1982) DNA methylation and gene activity: the adenovims system as a model. Cold Spring Harbor Symp Quant Biol 47: 593–603Google Scholar
  28. Doerfler W, Gahlmann R, Stabel S, Deuring R, Lichtenberg U, Schulz M, Eick D, Leisten R (1983) On the mechnism of recombination between adenoviral and cellular DNAs: The structure of junction sites. Curr Top Microbiol Immunol 109: 193–228CrossRefGoogle Scholar
  29. Doerfler W, Langner K-D, Knebel D, Weyer U, Dobrzanski P, Knust-Kron B (1985) Site-specific promoter methylations and gene inactivation. In: Cantoni GL, Razin A (eds) Biochemistry and Biology of DNA Methylation. Progress in Clinical and Biological Research, vol 198. Alan R. Liss, New York, pp 133–155Google Scholar
  30. Doerfler W, Spies A, Jessberger R, Lichtenberg U, Zock C, Rosahl T (1987) Recombination of foreign (viral) DNA with the host genome. Studies in vivo and in a cell-free system. In: Rott R, Goebel W (eds) Molecular basis of viral and microbial pathogenesis, 38th Mosbacher Kolloquium, 1987. Springer, Berlin Heidelberg New York Tokyo pp 60–72Google Scholar
  31. Doerfler W, Langner K-D, Knebel D, Müller U, Lichtenberg U, Weisshaar B, Renz D (1988a) Eukaryotic gene inactivation by sequence-specific promoter methylation and the release of the transcription block. In: Kahl G (ed) Architecture of eukaryotic genes. Verlag Chemie, Weinheim, pp 409–417Google Scholar
  32. Doerfler W, Weisshaar B, Hoeveler A, Knebel D, Müller U, Dobrzanski P, Lichtenberg U, Achten S, Hermann R (1988b) Promoter inhibition by DNA methylation: a reversible signal. Gene 74: 129–133PubMedCrossRefGoogle Scholar
  33. Dynan WS, Tjian R (1985) Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. Nature 316: 774–778PubMedCrossRefGoogle Scholar
  34. Doerfler W (1968) The fate of the DNA of adenovirus type 12 in baby hamster kidney cells. Proc Nati Acad Sci USA, 60: 636–643CrossRefGoogle Scholar
  35. Eick D, Fritz H-J, Doerfler W (1983) Quantitative determination of 5-methylcytosine in DNA by reverse-phase high-performance liquid chromatography. Anal Biochem 135: 165–171PubMedCrossRefGoogle Scholar
  36. Esche H (1982) Viral gene products in adenovirus type 2-transformed hamster cells. J Virol 41: 1076–1082PubMedGoogle Scholar
  37. Felsenfeld G, Nickol J, Behe M, McGhee J, Jackson D (1982) Methylation and chromatin structure. Cold Spring Harbor Symp Quant Biol 47: 593–603Google Scholar
  38. Gardiner-Gardner M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196: 261–282CrossRefGoogle Scholar
  39. Gjerset RA, Martin DW, Jr (1982) Presence of a DNA demethylating activity in the nucleus of murine erythroleukemia cells. J Biol Chem 257: 8581–8583PubMedGoogle Scholar
  40. Gorman CM (1985) High efficiency gene transfer into mammalian cells. In: Glover DM (ed) DNA cloning, vol. II. IRL Press, Oxford, Washington, pp 143–190Google Scholar
  41. Gorman CM, Moffat LF, Howard BH (1982) Recombinant genomes which express cloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 2: 1044–1051PubMedGoogle Scholar
  42. Groudine M, Eisenman R, Weintraub H (1981) Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation. Nature 292: 311–317PubMedCrossRefGoogle Scholar
  43. Günthert U, Schweiger M, Stupp M, Doerfler W (1976) DNA methylation in adenovirus, adenovirus-transformed cells, and host cells. Proc Nall Acad Sci USA 73: 3923–3927CrossRefGoogle Scholar
  44. Harland RM (1982) Inheritance of DNA methylation in microinjected eggs of Xenopus laevis. Proc Natl Acad Sci USA 79: 2323–2327PubMedCrossRefGoogle Scholar
  45. Harrington MA, Jones PA, Imagawa M, Kann M (1988) Cytosine methylation does not affect binding of transcription factor Spl. Proc Nall Acad Sci USA 85: 2066–2070CrossRefGoogle Scholar
  46. Hearing P, Shenk T (1983) The adenovirus type 5 ElA transcriptional control region contains a duplicate enhancer element. Cell 33: 695–703PubMedCrossRefGoogle Scholar
  47. Hermann R, Hoeveler A, Doerfler W (1989) Sequence-specific methylation in a downstream region of the late E2A promoter of adenovirus type 2 DNA interferes with protein binding. SubmittedGoogle Scholar
  48. Hoeveler A, Doerfler W (1987) Specific factors binding to the E2A late promoter region of adenovirus type 2 DNA: No apparent effects of 5’-CCGG-3’ methylation. DNA 6: 449–460PubMedCrossRefGoogle Scholar
  49. Miller M, Westin G, Jiricny J, Schaffner W (1988) Spl transcription factor binds DNA and activates transcription even when the binding site is CpG methylated. Genes and Development 2: 1127–1135CrossRefGoogle Scholar
  50. Jänner D, Jaenisch R (1985) Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature 315: 594–597CrossRefGoogle Scholar
  51. Johanssgn K, Persson,H, Lewis AM, Pettersson U, Tibbetts C, Philipson L (1978) Viral DNA sequences and gene products in hamster cells transformed by adenovirus type 2. J Viroi 27: 628–639Google Scholar
  52. Jones N, Shenk T (1979) An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc Nail Acad Sci USA 76: 3665–3669CrossRefGoogle Scholar
  53. Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20: 85–93PubMedCrossRefGoogle Scholar
  54. Kaye AM, Winocour E (1967) On the 5-methylcytosine found in the DNA extracted form polyoma virus. J Mol Biol 24: 475–478CrossRefGoogle Scholar
  55. Kelley DE, Pollock BA, Atchison ML, Perry RP (1988) The coupling between enhancer activity and hypomethylation of K immunoglobulin genes is developmentally regulated. Mol Cell Biol 8: 930–937PubMedGoogle Scholar
  56. Keshet I, Yisraeli J, Cedar H (1985) Effect of regional DNA methylation on gene expression. Proc Nail Acad Sci USA 82: 2560–2564CrossRefGoogle Scholar
  57. Keshet I, Lieman-Hurwitz J, Cedar H (1986) DNA methylation affects the formation of active chromatin. Cell 44: 535–543PubMedCrossRefGoogle Scholar
  58. Klimkait T, Doerfler W (1987) E1B functions of type C adenoviruses play a role in the complementation of blocked adenovirus type 12 DNA replication and late gene transcription in hamster cells. Virology 161: 109–120PubMedCrossRefGoogle Scholar
  59. Knebel D, Doerfler W (1986) N6-methyldeoxyadenosine residues at specific sites decrease the activity of the E1A promoter of adenovirus type 12 DNA. J Mol Biol 189: 371–375PubMedCrossRefGoogle Scholar
  60. Knebel D, Lübbert H, Doerfler W (1985) The promoter of the late p10 gene in the insect nuclear polyhedrosis virus Autographs califomica: Activation by viral gene products and sensitivity to DNA methylation. EMBO J 4: 1301–1306PubMedGoogle Scholar
  61. Knebel-Mörsdorf D, Achten S, Langner K-D, Rilger R, Fleckenstein B, Doerfler W (1988) Reactivation of the methylation-inhibited late E2A promoter of adenovirus type 2 DNA by a strong enhancer of human cytomegalovirus. Virology 166: 166–174PubMedCrossRefGoogle Scholar
  62. Knust B, Briiggemann U, Doerfler W (1989) Reactivation of a methylation-silenced gene in adenovirus-transformed cells by 5-azacytidine, by E1A transactivation or by continuous subcultivation. SubmittedGoogle Scholar
  63. Kovesdi I, Reichel R, Nevins JR (1987) Role of an adenovirus E2 promoter binding factor in El A-mediated coordinate gene control. Proc Natl Acad Sci USA 84: 2180–2184PubMedCrossRefGoogle Scholar
  64. Kruczek I, Doerfler W (1982) The unmethylated state of the promoter/leader and 5’-regions of integrated adenovirus genes correlates with gene expression. EMBO J 1: 409–414PubMedGoogle Scholar
  65. Kruczek I, Doerfler W (1983) 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 USA 80: 7586–7590Google Scholar
  66. Kuhlmann I, Doerfler W (1982) Shifts in the extent and patterns of DNA methylation upon explantation and subcultivation of adenovirus type 12-induced hamster tumor cells. Virology 118: 169–180PubMedCrossRefGoogle Scholar
  67. Kuhlmann I, Doerfler W (1983) Loss of viral genomes from hamster tumor cells and nonrandom alterations in patterns of methylation of integrated adenovirus type 12 DNA. J Virol 47: 631–636PubMedGoogle Scholar
  68. Kuhlmann I, Achten S, Rudolph R, Doerfler W (1982) Tumor induction by human adenovirus type 12 in hamsters: loss of the viral genome from adenovinrs type 12-induced tumor cells is compatible with tumor formation. EMBO J 1: 79–86PubMedGoogle Scholar
  69. Kunze R, Starlinger P, Schwartz D (1988) DNA methylation of the maize transposable element Ac interferes with its transcription. Mol Gen Genet 214: 325–327CrossRefGoogle Scholar
  70. Langner K-D, Vardimon L, Renz D, Doerfler W (1984) DNA methylations of three 5’ C-C-G-G 3’ sites in the promoter and 5’-region inactivate the E2a gene of adenovims type 2. Proc Natl Acad Sci USA 81: 2950–2954PubMedCrossRefGoogle Scholar
  71. Langner K-D, Weyer U, Doerfler W (1986) Trans effect of the El region of adenoviruses on the expression of a prokaryotic gene in mammalian cells: Resistance to 5’-CCGG-3’ methylation. Proc Natl Acad Sci USA 83: 1598–1602PubMedCrossRefGoogle Scholar
  72. Lichtenberg U, Zock C, Doerfler W (1987) Insertion of adenovirus type 12 DNA in the vicinity of an intracistemal A particle genome in Syrian hamster tumor cells. J Virol 61:2719–2726PubMedGoogle Scholar
  73. Lichtenberg U, Zock C, Doerfler W (1988) Integration of foreign DNA into mammalian genome can be associated with hypomethylation at site of insertion. Virus Res 11:335–342PubMedCrossRefGoogle Scholar
  74. Lübbert H, Doerfler W (1984) Transcription of overlapping sets of RNAs from the genome of Autographa califomica nuclear polyhedrosis virus: A novel method for mapping RNAs. J Virol 52: 255–265PubMedGoogle Scholar
  75. Maniatis T, Goodboum S, Fischer JA (1987) Regulation of inducible and tissue-specific gene expression. Science 236: 1237–1245PubMedCrossRefGoogle Scholar
  76. McClintock B (1951) Chromosome organization and genic expression. Cold Spring Harbor Symp Quant Biol 16: 13–47PubMedGoogle Scholar
  77. McClintock B (1964) Aspects of gene regulation in maize. Carnegie Inst Wash Year Book 63: 592–602Google Scholar
  78. McClintock B (1965) Components of action of the regulators Spm and Ac. Carnegie Inst Wash Year Book 64: 527–536Google Scholar
  79. McKnight S, Tjian R (1986) Transcriptional selectivity of viral genes in mammalian cells. Cell 46: 795–805PubMedCrossRefGoogle Scholar
  80. Muller U, Doerfler W (1987) Fixation of “unmethylated or 5’-CCGG-3’ methylated foreign DNA in the genome of hamster cells: gene expression and stability of methylation patterns. J Virol 61: 3710–3720PubMedGoogle Scholar
  81. Murray E, Grosveld F (1985) Methylation and ‘y-globin expression. In: Cantoni GL, Razin A (eds) Biochemistry and Biology of DNA Methylation. Alan R. Liss, New York, pp 157–176Google Scholar
  82. Nevins JR (1982) Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell 29: 913–919PubMedCrossRefGoogle Scholar
  83. Pfeifer GP, Drahovsky D (1986) DNA methyltransferase polypeptides in mouse and human cells. Biochim Biophys Acta 868: 238–242PubMedGoogle Scholar
  84. Pollack Y, Stein R, Razin A, Cedar H (1980) Methylation of foreign DNA sequences in eukaryotic cells. Proc Natl Acad Sci USA 77: 6463–6467PubMedCrossRefGoogle Scholar
  85. Razin A, Riggs AD (1980) DNA methylation and gene function. Science 210: 604–610PubMedCrossRefGoogle Scholar
  86. Razin A, Webb C, Szyf M, Yisraeli J, Rosenthal A, Naveh-Many T, Sciaky-Gallili N, Cedar H (1984) Variations in DNA methylation during mouse cell differentiation in vivo and in vitro. Proc Nail Acad Sci USA 81: 2275–2279CrossRefGoogle Scholar
  87. Razin A, Feldmesser E, Kafri T, Szyf M (1985) Cell specific DNA methylation patterns; formation and a nucleosome locking model for their function. In: Cantoni GL, Razin A (eds) Biochemistry and Biology of DNA Methylation. Progress in Clinical and Biological Research, vol 198. Alan R. Liss, New York, pp 239–253Google Scholar
  88. Razin A, Szyf M, Kafri T, Roll M, Giloh H, Scarpa S, Carotti D, Cantoni GL (1986) Replacement of 5-methylcytosine by cytosine: A possible mechanism for transient DNA demethylation during differentiation. Proc Natl Acad Sci USA 83: 2827–2831PubMedCrossRefGoogle Scholar
  89. Reichel R, Kovesdi I, Nevins JR (1987) Developmental control of a promoter-specific factor that is also regulated by the E1A gene product. Cell 48: 501–506PubMedCrossRefGoogle Scholar
  90. Reik W, Collick A, Norris ML, Barton SC, Surani MA (1987) Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature 328: 248–251PubMedCrossRefGoogle Scholar
  91. Roy PH, Weissbach A (1975) DNA methylase from HeLa cell nuclei. Nucleic Acids Res 2: 1669–1684PubMedCrossRefGoogle Scholar
  92. Saluz HP, Jiricny J, Jost JP (1986) Genomic sequencing reveals a positive correlation between the kinetics of strand-specific DNA methylation of the overlapping estradiol/glucocorticoid-receptor binding sites and the rate of avian vitellogenin mRNA synthesis. Proc Natl Acad Sci USA 83: 7167–7171PubMedCrossRefGoogle Scholar
  93. Schuster AM, Burbank DE, Meister B, Skrdla MP, Meints RH, Hattman S, Swinton D, van Etten JL (1986) Characterization of viruses infecting a eukaryotic Chlorella-like green alga. Virology 150: 170–177PubMedCrossRefGoogle Scholar
  94. Schwartz D, Dennis E (1986) Transposase activity of the Ac controlling element in maize is regulated by its degree of methylation. Mol Gen Genet 205: 476–482CrossRefGoogle Scholar
  95. Simon D, Gnmert F, v. Acken U, Döring HP, Kröger H (1978) DNA-methylase from regenerating rat liver: purification and characterisation. Nucleic Acids Res 5: 2153–2167Google Scholar
  96. Smith SS, Hardy TA, Baker DJ (1987) Human DNA (cytosine-5) methyltransferase selectively methylates duplex DNA containing mispairs. Nucleic Acids Res 15: 6899–6916PubMedCrossRefGoogle Scholar
  97. Southern EM (1975) Detection of sepcific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503–517PubMedCrossRefGoogle Scholar
  98. Southern PJ, Berg P (1982) Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Gen 1: 327–341Google Scholar
  99. Stein R, Gruenbaum Y, Pollack Y, Razin A, Cedar H (1982) Clonal inheritance of the pattern of DNA methylation in mouse cells. Proc Natl Acad Sci USA 79: 61–65PubMedCrossRefGoogle Scholar
  100. Supakar PC, Weist D, Zhang D, InamadarN, Zhang XY, Khan R, Ehrlich KC, Ehrlich M (1988) Methylated DNA-binding protein is present in various mammalian cell types. Nucl Acids Res 16: 8029–8043Google Scholar
  101. Sutter D, Doerfler W (1979) Methylation of integrated viral DNA sequences in hamster cells transformed by adenovirus 12. Cold Spring Harbor Symp Quant Biol 44: 565–568Google Scholar
  102. Sutter D, Doerfler W (1980) Methylation of integrated adenovirus type 12 DNA sequences in transformed cells is inversely correlated with viral gene expression. Proc Natl Acad Sci USA 77: 253–256PubMedCrossRefGoogle Scholar
  103. Sutter D, Westphal M, Doerfler W (1978) Patterns of integration of viral DNA sequences in the genomes of adenovirus type 12-transfomted hamster cells. Cell 14: 569–585PubMedCrossRefGoogle Scholar
  104. Swain JL, Stewart TA, Leder P (1987) Parental legacy determines methylation and expression of an autosomal transgene: A molecular mechanism for parental imprinting. Cell 50: 719–727PubMedCrossRefGoogle Scholar
  105. Thompson JP, Granoff A, Willis DB (1986) Trans-activation of a methylated adenovirus promoter by a frog virus 3 protein. Proc Natl Acad Sci USA 83: 7688–7692PubMedCrossRefGoogle Scholar
  106. Tjia ST, Carstens EB, Doerfler W (1979) Infection of Spodoptera frugiperda cells with Autographa califomica nuclear polyhedrosis virus. II. The viral DNA and the kinetics of its replication. Virology 99: 399–409PubMedCrossRefGoogle Scholar
  107. Van Etten JL, Burbank DE, Schuster AM, Meints RH (1985) Lytic viruses infecting a Chlorella-like alga. Virology 140: 135–143PubMedCrossRefGoogle Scholar
  108. Vardimon L, Doerfler W (1981) Patterns of integration of viral DNA in adenovirus type 2-transformed hamster cells. J Mol Biol 147: 227–246PubMedCrossRefGoogle Scholar
  109. Vardimon L, Neumann R, Kuhlmann I, Sutter D, Doerfler W (1980) DNA methylation and viral gene expression in adenovirus transformed and -infected cells. Nucleic Acids Res 8: 2461–2473PubMedCrossRefGoogle Scholar
  110. Vardimon L, Günthert U, Doerfler W (1982a) In vitro methylation of the BsuRI (5’-GGCC-3’) sites in the E2a region of adenovirus type 2 DNA does not affect expression in Xenopus laevis oocytes. Mol Cell Biol 2: 1574–1580PubMedGoogle Scholar
  111. Vardimon L, Kressmann A, Cedar H, Maechler M, Doerfler W (1982b) Expression of a cloned adenovirus gene is inhibited by in vitro methylation. Proc Natl Acad Sci USA 79: 1073–1077PubMedCrossRefGoogle Scholar
  112. Waalwijk C, Flavell RA (1978) MspI, an isoschizomer of HpaII which cleaves both unmethylated and methylated Hpall sites. Nucleic Acids Res 5: 3231–3236PubMedCrossRefGoogle Scholar
  113. Wagner H, Simon D, Werner E, Gelderblom H, Darai C, Flügel RM (1985) Methylation pattern of fish lymphocystis disease virus DNA. J Virol 53: 1005–1007PubMedGoogle Scholar
  114. Wang RY-H, Zhang X-Y, Ehrlich M (1986) A human DNA-binding protein is methylation-specific and sequence-specific. Nucleic Acids Res 14: 1599–1614PubMedCrossRefGoogle Scholar
  115. Ward C, Bolden A, Nalin CM, Weissbach A (1987) In vitro methylation of the 5’-flanking regions of the mouse ß-globin gene. J Biol Chem 262: 11057–11063PubMedGoogle Scholar
  116. Watt F, Molloy PL (1988) Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus late promoter. Genes and Development 2: 1136–1143PubMedCrossRefGoogle Scholar
  117. Weisshaar B, Langner K-D, Jüttermann R, Müller U, Zock C, Klimkait T, Doerfier W (1988) Reactivation of the methylation-inactivated late E2A promoter of adenovirus type 2 by E1A (13S) functions. J Mol Biol 202: 255–270PubMedCrossRefGoogle Scholar
  118. Wienhues U, Doerfler W (1985) Lack of evidence for methylation of parental and newly synthesized adenovirus type 2 DNA in productive infections. J Virol 56: 320–324PubMedGoogle Scholar
  119. Wigler M, Levy D, Perucho M (1981) The somatic replication of DNA methylation. Cell 24: 33–40PubMedCrossRefGoogle Scholar
  120. Willis DB, Granoff A (1980) Frog virus 3 DNA is heavily methylated at CpG sequences. Virology 107: 250–257PubMedCrossRefGoogle Scholar
  121. Willis DB, Goorha R, Granoff A (1984) DNA methyltransferase induced by frog virus 3. J Virol 49: 86–91PubMedGoogle Scholar
  122. Willis DB, Goorha R, Chinchar VG (1985) Macromolecular synthesis in cells infected by frog virus 3. Curr Top Microbiol Immunol 116: 77–106PubMedCrossRefGoogle Scholar
  123. Woodcock DM, Crowther PJ, Diver WP (1987) The majority of methylated deoxycytidines in human DNA are not in the CpG dinucleotide. Biochem Biophys Res Commun 145: 888–894PubMedCrossRefGoogle Scholar
  124. Xia Y, Burbank DE, van Etten JL (1986) Restriction endonuclease activity induced by NC-1A virus infection of a Chlorella-like green alga. Nucleic Acids Res 14: 6017–6030PubMedCrossRefGoogle Scholar
  125. Yisraeli J, Adelstein RS, Melloul D, Nudel U, Yaffe H, Cedar H (1986) Muscle-specific activation of a methylated chimeric actin gene. Cell 46: 409–416PubMedCrossRefGoogle Scholar
  126. Zhang X-Y, Ehrlich KC, Wang R Y-H, Ehrlich M (1986) Effect of site-specific DNA methylation and mutagenesis on recognition by methylated DNA-binding protein from human placenta. Nucleic Acids Res 14: 8387–8397PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Walter Doerfler
    • 1
  1. 1.Institut für GenetikUniversität zu KölnKöln 41Germany

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