Summary
Eukaryotic genomes contain 5-methylcytosine (5mC) as a rare base. 5mC arises by postsynthetic modification of cytosine and occurs, at least in animals, predominantly in the dinucleotide CpG. The base is not distributed randomly in these genomes but conforms to a pattern. This pattern varies between taxa but appears to be inherited in a semi-conservative fashion. At the level of the genome, gross changes in the level of DNA methylation have been noted. This has encouraged speculation that the modification may play a role in cellular differentiation. Tissue-specific patterns of DNA methylation, predicted by various models of differentiation, have been found for most vertebrate genes so far examined. A correlation has emerged between the undermethylation of these regions and their transcription, but this is not always the case. While data for eukaryotic viral sequences are less equivocal, studies of this kind cannot in isolation distinguish between undermethylation being a cause or a consequence of gene activity. If it were a cause, it is probable that the demethylation of specific CpG sites would be a necessary yet not a sufficient condition for transcription to occur. The introduction of artificially methylated DNA sequences into individual eukaryotic cells by microinjection or transformation may provide the means to elucidate these questions in the future. In the meantime, the study of eukaryotic DNA methylation promises to contribute much to our understanding of the regulation of gene expression in these organisms.
Similar content being viewed by others
References
Adams RLP, McKay EL, Craig LM, Burdon RH (1979) Methylation of Mosquito DNA. Biochim Biophys Acta 563:72–81
Adams RLP, Burdon RH, Gibb S, McKay EL (1981) DNA methylase during development of Xenopus laevis. Biochem Soc Trans 9: 255P
Adams RLP, Burdon RH, Fulton J (1983) Methylation of satellite DNA. Biochem Biophys Res Commun 113:695–702
Andrews GK, Dziadek M, Tamaoki T (1982) Expression and methylation of the mouse α-fetoprotein gene in embryonic, adult and neoplastic tissues. J Biol Chem 257:5148–5153
Avakyan KA, Zhizhina GP, Parkhomenko II (1979) Secondary structure and methylation of DNA in transplantable tumors and cultures of embryonic cells transformed by oncogenic viruses. Biochemistry New York 44:1132–1135
Baur R, Wohlert H, Kröger H (1979) Methylation of DNA in developing embryos of the sea urchin Psammechinus miliaris. Hoppe-Seyler's Z Physiol Chem 360:1263–1269
Behe M, Felsenfeld G (1981) Effects of methylation on a synthetic polynucleotide: The B-Z transition in poly(dG-m5dC)· poly (dG-m5dC). Proc Natl Acad Sci USA 78:1619–1623
Bird AP (1978) Use of restriction enzymes to study eukaryotic DNA methylation: II. The symmetry of the methylated sites supports semi-conservative copying of the methylation patterns. J Mol Biol 118:49–60
Bird AP, Southern EM (1978) Use of restriction enzymes to study eukaryotic DNA methylation: I. The methylation pattern in ribosomal DNA from Xenopus laevis. J Mol Biol 118:27–47
Bird AP, Taggart MH, Smith BA (1979) Methylated and unmethylated DNA compartments in the sea urchin genome. Cell 17:889–901
Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8:1499–1504
Bird AP, Taggart MH (1980) Variable patterns of total DNA and rDNA methylation in animals. Nucleic Acids Res 8:1485–1497
Bird AP, Taggart MH, Gehring CA (1981a) Methylated and unmethylated ribosomal RNA genes in the mouse. J Mol Biol 152:1–17
Bird AP, Taggart MH, MacLeod D (1981b) Loss of rDNA methylation accompanies the onset of ribosomal gene activity in early development of Xenopus laevis. Cell 26:381–390
Bird AP (1983) DNA Modification. Chapter 4. In: MacLean M, Gregory SP, Flavell RA (eds) Eukaryotic genes: their structure, activity and regulation. Butterworths, Sevenoaks
Bolen PL, Grant DM, Swinton D, Boynton JE, Gillham NW (1982) Extensive methylation of chloroplast DNA by a nuclear gene mutation does not affect chloroplast gene transmission in Chlamydomonas. Cell 28:335–343
Bower DJ, Errington LH, Cooper DN, Morris S, Clayton RM (1983) Chicken lens δ-crystallin gene expression and methylation in several non-lens tissues. Nucleic Acids Res 11:2513–2527
Boyd AW, Schrader JW (1982) Derivation of macrophage-like lines from the pre-B lymphoma ABLS 8.1 using 5 azacytidine. Nature 297:691–693
Breznik T, Cohen JC (1982) Altered methylation of endogenous viral promoter sequences during mammary carcinogenesis. Nature 295:255–257
Browne MJ, Burdon RH (1977) The sequence specificity of vertebrate DNA methylation. Nucleic Acids Res 4:1025–1037
Browne MJ, Turnbull JF, McKay EL, Adams RLP, Burdon RH (1977) The sequence specificity of a mammalian DNA methylase. Nucleic Acids Res 4:1039–1045
Browne MJ, Cato ACD, Burdon RH (1978) The distribution of modified and non-modified C-G doublets in BHK-21 cell DNA. FEBS Letts 91:69–73
Bugler B, Bertaux O, Valencia R (1980) Nucleic acids methylation of synchronized BHK 21 HS 5 fibroblasts during the mitotic phase. J Cell Physiol 103:149–157
Burdon RH, Adams RLP (1969) The in vivo methylation of DNA in mouse fibroblasts. Biochim Biophys Acta 174:322–329
Burdon RH, Adams RLP (1980) Eukaryotic DNA methylation. Trends Biochem Sci 5:294–297
Burtseva NN, Azizov YM, Vanyushin BF (1979) Tissue specificity of the decrease in methylation of DNA of cattle lymphocytes in chronic lympholeukemia. Biochemistry New York 14:1021–1026
Busslinger M, de Boer E, Wright S, Grosveld FG, Flavell RA (1983) The sequence GGCmCGG is resistant to MspI cleavage. Nucleic Acids Res 11:3559–3569
Castora FJ, Arnheim N, Simpson MV (1980) Mitochondrial DNA polymorphism: evidence that variants detected by restriction enzymes differ in nucleotide sequence rather than in methylation. Proc Natl Acad Sci USA 77:6415–6419
Cate RL, Chick W, Gilbert W (1983) Comparison of the methylation patterns of the two rat insulin genes. J Biol Chem 258:6645–6652
Cato ACB, Adams RLP, Burdon RH (1978) Genome modification in two lines of baby hamster kidney fibroblasts (BHK-21). Biochim Biophys Acta 521:397–406
Cedar H, Solage A, Glaser G, Razin A (1979) Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. Nucleic Acids Res 6:2125–2132
Chapman VM, Kratzer PG, Siracusa LD, Quarantillo BA, Evans R, Liskay RM (1982) Evidence for DNA modification in the maintenance of X-chromosome inactivation of adult mouse tissues. Proc Natl Acad Sci USA 79:5357–5361
Chen M-J, Nienhuis AW (1981) Structure and expression of human globin genes introduced into mouse fibroblasts. J Biol Chem 256:9680–9683
Chen YT, Negishi M, Nebert DW (1982) Cytochrome-P1-450 structural gene in mouse, rat and rabbit—differences in DNA methylation and developmental expression of messenger RNA. DNA 1:231–238
Christman JK, Weich N, Schoenbrun B, Schneiderman N, Acs G (1980) Hypomethylation of DNA during differentiation of Friend erythroleukemia cells. J Cell Biol 86:366–370
Christy B, Scangos G (1982) Expression of transferred thymidine kinase genes is controlled by methylation. Proc Natl Acad Sci USA 79:6299–6303
Clark CG (1980) The distribution of 5-methylcytosine in the DNA of plants. Honours Thesis, University of Edinburgh
Clough DW, Kunkel LM, Davidson RL (1982) 5-azacytidine-induced reactivation of a Herpes Simplex thymidine kinase gene. Science 216:70–73
Cohen JC (1980) Methylation of milk-bourne and genetically transmitted mouse mammary tumor virus proviral DNA. Cell 19:653–662
Colgan V, Elbrecht A, Goldman P, Lazier CB, Deeley R (1982) The avian apoprotein II very low density lipoprotein gene. Methylation patterns of 5′ and 3′ flanking regions during development and following induction by estrogen. J Biol Chem 257:14453–14460
Compere SJ, Palmiter RD (1981) DNA methylation controls the inducibility of the mouse metallothionein-I gene in lymphoid cells. Cell 25:233–240
Cooper DN, Taggart MH, Bird AP (1983a) Unmethylated domains in vertebrate DNA. Nucleic Acids Res 11:647–658
Cooper DN, Errington LH, Clayton RM (1983b) Variation in the DNA methylation pattern of expressed and non-expressed genes in chicken. DNA 2:131–140
Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775–780
Creusot F, Christman JK (1981) Localisation of DNA methyltransferase in the chromatin of Friend erythroleukaemia cells. Nucleic Acids Res 9:5359–5381
Creusot F, Acs G, Christman KJ (1982a) Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-Azacytidine and 5-Aza-2′-deoxycytidine. J Biol Chem 257:2041–2048
Creusot F, Schneiderman N, Herzog D, Acs G, Christman JK (1982b) Effect of 5-azadeoxycytidine on differentiation and DNA methylation of Friend erythroleukaemia cells: cytidine analogue inhibition of DNA methyltransferase. Biol Cell 45:96
Culp LA, Dore E, Brown GM (1970) Methylated bases in DNA of animal origin. Arch Biochem Biophys 136:73–79
Dawid IB, Brown DD, Reeder RH (1970) Composition and structure of chromosomal and amplified ribosomal DNAs of Xenopus laevis. J Mol Biol 51:341–360
Dawid IB (1974) 5-Methylcytidylic acid: absence from mitochondrial DNA of frogs and HeLa cells. Science 184:80–81
Dean MC, Sonenshein GE (1982) Expression of aberrant IgA RNA species in mouse myeloma cells appears to corrlate with DNA rearrangement and methylation. J Cell Biol 95:473
Desrosiers RC, Mulder C, Fleckenstein B (1979) Methylation of Herpes saimiri DNA in lymphoid tumor cell lines. Proc Natl Acad Sci USA 76:3839–3843
Desrosiers RC (1982) Specifically unmethylated cytidylic-guanylate sites in Herpes virus saimiri in tumor cells. J Virol 43:427–435
Dickinson DG, Baker RF (1978) Evidence for translocation of DNA sequences during sea urchin embryogenesis. Proc Natl Acad Sci USA 75:5627–5630
Doskočil J, Šorm F (1962) Distribution of 5-methylcytosine in pyrimidine sequences of deoxyribonucleic acids. Biochim Biophys Acta 55:953–959
Drahovsky D Morris NR (1971) Mechanisms of action of rat liver DNA methylase. I. Interaction with double-stranded methylacceptor DNA. J Mol Biol 57:475–489
Drahovsky D, Kaul S, Boehm TLJ, Wacker A (1978) Enzymatic DNA methylation in somatic cell hybrids. Hoppe-Seyler's Z Physiol Chem 359:1076
Drahovsky D, Boehm TLJ (1980) Enzymatic DNA methylation in higher eukaryotes. Int J Biochem 12:523–528
Drohan WN, Benede LE, Graham DE, Smith GH (1982) Mouse mammary tumor virus proviral sequences congenital to C3H/5m mice are differentially hypomethylated in chemically induced, virus-induced, and spontaneous mammary tumors. J Virol 43:876–884
Dyer TA (1982) Methylation of chloroplasts DNA in Chlamydomonas. Nature 298:422–423
Eastman EM, Goodman RM, Erlanger BF, Miller OJ (1980) 5-Methylcytosine in the DNA of the polytene chromosomes of the diptera Sciara coprophila, Drosophila melanogaster and D. persimilis. Chromosoma 79:225–239
Eden FC, Musti AM, Sobieski DA (1981) Clusters of repeated sequences of chicken DNA are extensively methylated but contain specific undermethylated regions. J Mol Biol 148:129–151
Ehrlich M, Wang YH (1981) 5-Methylcytosine in eukaryotic DNA. Science 212:1350–1357
Ehrlich M, Gama-Sosa M, Huang L-H, Midgett RM, Kuo KC, McCune RA, Gehrke C (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues or cells. Nucleic Acids Res 10:2709–2721
Elgin SCR (1981) DNaseI-hypersensitive sites of chromatin. Cell 27:413–415
Errington LH, Cooper DN, Clayton RM (1983) The patterns of DNA methylation in the δ-crystallin genes in transdifferentiating neural retina cultures. Differentiation 24:33–38
Etkind PR, Sarkar NH (1983) Integration of new endogenous mouse mammary tumor virus proviral DNA at common sites in the DNA of mammary tumors of C3Hf mice and hypomethylation of the endogenous mouse mammary tumor virus proviral DNA in C3Hf mammary tumors and spleens. J Virol 45:114–123
Fedoroff NV, Brown DD (1978) The nucleotide sequence of oocyte 5S DNA in Xenopus laevis. I. The AT-rich spacer. Cell 13:701–716
Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92
Felsenfeld G, McGhee J (1982) DNA methylation and gene control. Nature 296:602–603
Felsenfeld G, Nickol J, Behe M, McGhee J, Jackson D (1983) Methylation and chromatin structure. Cold Spring Harbour Symp Quant Biol 47:577–584
Ferraro M, Lavia P (1982) rDNA demethylation and ribosomal genes expression in human cells. Biol Cell 45:173
Fisher EF, Caruthers MH (1979) Studies on gene control regions. XII. The functional significance of a Lac operator constitutive mutation. Nucleic Acids Res 7:401–416
Fradin A, Manley JL, Prives CL (1982) Methylation of simian virus 40 HpaII site affects late, but not early viral gene expression. Proc Natl Acad Sci USA 79:5142–5146
Gama-Sosa MA, Wang RY-H, Kuo KC, Gehrke CW, Ehrlich M (1983) The 5-methylcytosine content of highly repeated sequences in human DNA. Nucleic Acids Res 11:3087–3095
Gantt RR (1974) Is aberrant nucleic acid methylation related to malignant transformation? J Natl Cancer Inst 53:1505–1508
Gautier F, Bunemann H, Grotjahn L (1977) Analysis of calfthymus satellite DNA: evidence for specific methylation of cytosine in CG sequences. Eur J Biochem 80:175–183
Gautsch JW, Wilson MC (1983) Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression. Nature 301:32–37
Geraci D, Eremenko T, Cocchiara R, Granieri A, Scarano E, Volpe P (1974) Correlation between synthesis and methylation of DNA in HeLa cells. Biochem Biophys Res Commun 57:353–358
Gerber-Huber S, May FEB, Westley BR, Felber BK, Hosbach HA, Andres A-C, Ryffel GU (1983) In contrast to other Xenopus genes the estrogen-inducible vitellogenin genes are expressed when totally methylated. Cell 33:43–51
Gjerset RA, Martin DW (1982) Presence of a DNA demethylating activity in the nucleus of murine erythroleukemic cells. J Biol Chem 257:8581–8583
Goldsbrough PB, Ellis THN, Lomonossoff GP (1982) Sequence variation and methylation of the flax 5S RNA genes. Nucleic Acids Res 10:4501–4514
Graves JAM (1982) 5-Azacytidine-induced reexpression of alleles on the inactive X chromosome in a hybrid mouse cell line. Exp Cell Res 141:99–105
Grippo P, Iaccarino M, Parisi E, Scarano E (1968) Methylation of DNA in developing sea urchin embryos. J Mol Biol 36:195–208
Groffen J, Heisterkamp N, Blennerhasset G, Stephenson JR (1983) Regulation of viral and cellular oncogene expression by cytosine methylation. Virology 126:213–227
Groot GSP, Kroon AM (1979) Mitochondrial DNA from various organisms does not contain internally methylated cytosine in-CCGG-sequences. Biochim Biophys Acta 564:355–357
Groudine M, Eisenman R, Weintraub H (1981) Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation. Nature 292:311–317
Gruenbaum Y, Naveh-Many T, Cedar H, Razin A (1981a) Sequence specificity of methylation in higher plant DNA. Nature 292:860–862
Gruenbaum Y, Cedar H, Razin A (1981b) Restriction enzyme digestion of hemimethylated DNA. Nucleic Acids Res 9:2509–2515
Gruenbaum Y, Stein R, Cedar H, Razin A (1981c) Methylation of CpG sequences in eukaryotic DNA. FEBS Letts 124:67–71
Gruenbaum Y, Cedar H, Razin A (1982) Substrate and sequence specificity of a eukaryotic DNA methylase. Nature 295:620–622
Guntaka RV, Rao PY, Mitsialis SA, Katz R (1980) Modification of avian sarcoma proviral DNA sequences in non-permissive XC cells but not in permissive chicken cells. J Virol 34:569–572
Gunthert U, Schweiger M, Stupp M, Doerfler W (1976) DNA methylation in adenovirus, adenovirus transformed cells and host cells. Proc Natl Acad Sci USA 73:3923–3927
Guseinov VA, Kiryanov GI, Vanyushin BF (1975) Intragenome distribution of 5-methylcytosine in DNA of healthy and wiltinfected, cotton plant (Gossypium hirsutum L.). Mol Biol Rep 2:59–63
Haigh LS, Owens BB, Hellewell S, Ingram VM (1982) DNA methylation in chicken α-globin gene expression. Proc Natl Acad Sci USA 79:5332–5336
Harbers K, Karbers B, Spencer JH (1975) Nucleotide clusters in deoxyribonucleic acids. XII. The distribution of 5-methylcytosine in pyrimidine oligonucleotides of mouse L-cell satellite DNA and main band DNA. Biochem Biophys Res Commun 66:738–746
Harbers K, Schnieke A, Stuhlmann H, Jähner O, Jaenisch R (1981) DNA methylation and gene expression: Endogenous retroviral genome becomes infectious after molecular cloning. Proc Natl Acad Sci USA 78:7609–7613
Harland R (1981) Initiation of DNA replication in eukaryotic chromosomes. Trends Biochem Sci 6:71–74
Harland RM (1982) Inheritance of DNA methylation in microinjected eggs of Xenopus laevis. Proc Natl Acad Sci USA 79:2323–2327
Harrison CMH (1971) The arrangement of chromatin in the interphase nucleus with reference to cell differentiation and repression in higher organisms. Tissue Cell 3:523–550
Hattman S, Kenny X, Berger L, Pratt K (1978) Comparative study of DNA methylation in three unicellular eukaryotes. J Bacteriol 135:1156–1157
Hjelle BL, Phillips JA, Seeburg PH (1982) Relative levels of methylation in human growth hormone and chorionic somatomammotropin genes in expressing and non-expressing tissues. Nucleic Acids Res 10:3459–3474
Hoffman JW, Steffen D, Gusella J, Tabin C, Bird S, Cowing D, Weinberg RA (1982) DNA methylation affecting the expression of murine leukemia proviruses. J Virol 44:144–157
Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232
Hörz W, Altenburger W (1981) Nucleotide sequence of mouse satellite DNA. Nucleic Acids Res 9:683–696
Hotchkiss RD (1948) The quantitative separation of nurines, pyrimidines and nucleosides by paper chromatography. J Biol Chem 175:315–332
Hotta Y, Hecht N (1971) Methylation of Lilium DNA during the meiotic cycle. Biochim Biophys Acta 238:50–59
Hynes NE, Rahmsdorf U, Kennedy N, Fabiani L, Michalides R, Nusse R, Groner B (1981) Structure, stability, methylation, expression and glucocorticoid induction of endogenous and transfected proviral genes of mouse mammary tumor virus in mouse fibroblasts. Gene, 15:307–317
Ivarie RD, Morris JA (1982) Induction of prolactin-deficient variants of GH3 rate pituitary tumor cells by ethyl methanesulfonate: Reversion by 5-azacytidine, a DNA methylation inhibitor. Proc Natl Acad Sci USA 79:2967–2970
Jaenisch R, Harbers K, Jähner D, Stewart C, Stuhlmann H (1982) DNA methylation, retroviruses, and embryogenesis. J Cell Biolchem 20:331–336
Jähner D, Stuhlmann H, Stewart CL, Harbers K, Lohler J, Simon I, Jaenisch R (1982) De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature 298:623–628
Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogues and DNA methylation. Cell 20:85–93
Jones PA, Taylor SM (1981) Hemimethylated duplex DNAs prepared from 5-azacytidine-treated cells. Nucleic Acids Res 9:2933–2947
Jones PA, Taylor SM, Mohandas T, Shapiro LJ (1982) Cell cyclespecific reactivation of an inactive X-chromosome locus by 5-azadeoxycytidine. Proc Natl Acad Sci USA 79:1215–1219
Jones RE, DeFeo D, Piatigorsky J (1981) Transcription and sitespecific hypomethylation of the δ-crystallin genes in the embryonic chicken lens. J Biol Chem 256:8172–8176
Josse J, Kaiser AD, Kornberg A (1961) Enzymatic synthesis of deoxyribonucleic acid. VIII. Frequencies of nearest neighbor base sequences in deoxyribonucleic acid. J Biol Chem 236:864–875
Kappler JW (1970) The kinetics of DNA methylation in cultures of a mouse adrenal cell line. J Cell Physiol 75:21–32
Kappler JW (1971) The 5-methylcytosine content of DNA: tissue specificity. J Cell Physiol 78:33–36
Kastan MB, Gowans BJ, Lieberman MW (1982) Methylation of deoxycytidine incorporated by excision-repair synthesis of DNA. Cell 30:509–516
Keene MA, Corces V, Lowenhaupt K, Elgin SCR (1981) DNaseI hypersensitive sites in Drosophila chromatin occur at the 5′ ends of regions of transcription. Proc Natl Acad Sci USA 78:143–146
Keshet E, Cedar H (1983) Effect of CpG methylation on MspI. Nucleic Acids Res 11:3571–3580
Kintner C, Sugden B (1981) Conservation and progressive methylation of Epstein-Barr viral DNA sequences in transformed cells. J Virol 38:305–316
Korba BE, Hays JB (1982) Partially deficient methylation of cytosine in DNA at CC TA GG sites stimulates genetic recombination of Bacteriophage Lambda. Cell 28:531–541
Korn LJ, Gurdon JB (1981) The reactivation of developmentally inert 5S genes in somatic nuclei injected into Xenopus oocytes. Nature 289:461–465
Kratzer PG, Chapman VM, Lambert H, Evans RE, Liskay RM (1983) Differences in the DNA of the inactive X-chromosomes of fetal and extraembryonic tissues of mice. Cell 33:37–42
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 1:409–414
Kunnath L, Locker J (1982) Variable methylation of the ribosomal RNA genes of the rat. Nucleic Acids Res 10:3877–3892
Kunnath L, Locker J (1983) Developmental changes in the methylation of the rat albumin and α-fetoprotein genes. EMBO J 2:317–324
Kuo MT, Mandel JL, Chambon P (1979) DNA methylation: correlation with DNaseI sensitivity of chicken ovalbumin and conalbumin chromatin. Nucleic Acids Res 7:2105–2113
LaVolpe A, Taggart M, MacLeod D, Bird A (1983) Coupled demethylation of sites in a conserved sequence of Xenopus ribosomal DNA. Cold Spring Harbour Symp Quant Biol 47:585–592
Lapeyre J, Becker FF (1979) 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem Biophys Res Commun 87:698–705
Levine M, Garen A, Lepesant JA, Lepesant-Kejzlarova J (1981) Constancy of somatic DNA organization in developmentally regulated regions of the Drosophila genome. Proc Natl Acad Sci USA 78:2417–2421
Ley TJ, De Simone J, Anagnou NP, Keller GH, Humphries RK, Turner PH, Young NS, Heller P, Nienhuis AW, (1982) 5-Azacytidine selectively increases γ-globin synthesis in a patient with β+ thalassemia. New Engl J Med 307:1469–1475
McCelland M (1981) The effect of sequence specific DNA methylation on restriction endonuclease cleavage. Nucleic Acids Res 9:5859–5866
McClelland M, Ivarie R (1982) Asymmetrical distribution of CpG in an “average” mammalian gene Nucleic Acids Res 10:7865–7877
McGeady ML, Jhappan C, Ascione R, Vande Woude GF (1983) In vitro methylation of specific regions of the cloned moloney sarcoma virus genome inhibits its transforming activity. Mol Cell Biol 3:305–314
McGhee JD, Ginder GD (1979) Specific DNA methylation sites in the vicinity of the chicken β-globin genes. Nature 280:419–420
McKeon C, Ohkubo H, Paston I, de Crombrugghe B (1982) Unusual methylation pattern of the α2(1) collagen gene. Cell 29:203–210
MacLeod D, Bird A (1981) DNase I sensitivity and methylation of active versus inactive rRNA genes in Xenopus species hybrids. Cell 29:211–218
Magnaval R, Bertaux O, Pourci ML, Valencia R (1981) Methylation and synthesis of chromatin fractions in normal vitamin B12-deprived and-restored Euglena cells. Biochem Soc Trans 9:130
Mandel JL, Chambon P (1979) DNA methylation: organ specific variations in the methylation pattern within and around ovalbumin and other chicken genes. Nucleic Acids Res 7:2081–2103
Manes C, Menzel P (1981) Demethylation of CpG sites in DNA of early rabbit trophoblast. Nature 293:589–590
Mann MB, Smith HO (1977) Specificity of HpaII and HaeII DNA methylases. Nucleic Acids Res 4:4211–4221
Marcaud L, Reynaud C-A, Therwath A, Scherrer K (1981) Modification of the methylation pattern in the vicinity of the chicken globin genes in avian erythroblastosis virus transformed cells. Nucleic Acids Res 9:1841–1851
Martin GR (1982) X-chromosome inactivation in mammals. Cell 29:721–724
Mays-Hoopes LL (1982) Methylation and rearrangement of mouse intracisternal A particle genes in development, aging and cancer. J Cell Biol 95:216
Meijlink FCPW, Philipsen JNJ, Gruber M, Geert AB (1983) Methylation of the chicken vitellogenin gene: influence of estradiol administration. Nucleic Acids Res 11:1361–1373
Mermod J-J, Bourgeois S, Defer N, Crépin M (1983) Demethylation and expression of murine mammary tumor proviruses in mouse thymoma cell lines. Proc Natl Acad Sci USA 80:110–114
Meselson M, Yuan R, Heywood J (1972) Restriction modification enzyme systems in bacteria. Ann Rev Biochem 41:447–466
Migeon BR, Wolf SF, Marini C, Axelman J (1982) Derepression with decreased expression of the G6PD locus on the inactive X chromosome in normal human cells. Cell 29:595–600
Miller OJ, Schnedl W, Allen J, Erlanger BF (1974) 5-Methylcytosine localised in mammalian constitutive heterochromatin. Nature 251:636–637
Miller DA, Okamoto E, Erlanger BF, Miller OJ (1982) Is DNA methylation responsible for mammalian X-chromosome inactivation? Cytogenet Cell Genet 33:345–349
Miller RH, Robinson WS (1983) Integrated hepatitus B virus DNA sequences specifying the major viral core polypeptide are methylated in PLC/PRF/5 cells. Proc Natl Acad Sci USA 80:2534–2538
Mohandas T, Sparkes RS, Shapiro LJ (1981) Reactivation of an inactive human X-chromosome: evidence for X-inactivation by DNA methylation. Science 211:393–396
Molitor H, Drahovsky D, Wacker A (1976) Unmethylated DNA in mouse L cells. 1. DNA fibre autoradiography. Biochim Biophys Acta 432:28–36
Montandon PE, Montandon F, Fan H (1982) Methylation state and DNase I sensitivity of chromatin containing Moloney and Murine Leukemia virus DNA in exogenously infected mouse cells. J Virol 44:475–486
Nakhasi HL, Lynch KR, Dolan KP, Unterman RD, Feigelson P (1981) Covalent modification and repressed transcription of a gene in hepatoma cells. Proc Natl Acad Sci USA 78:834–837
Nass MMK (1973) Differential methylation of mitochondrial and nuclear DNA in cultured mouse, hamster and virus transformed hamster cells. In vivo and in vitro methylation. J Mol Biol 80:155–175
Naveh-Many T, Cedar H (1981) Active gene sequences are undermethylated. Proc Natl Acad Sci USA 78:4246–4250
Naveh-Many T, Cedar H (1982) Topographical distribution of 5-methylcytosine in animal and plant DNA. Mol Cell Biol 2:758–762
Nishio A, Uyeki EM (1982) Nuclease sensitivity of methylated DNA as a probe for chromatin reconstitution by genotoxicants. Biochem Biophys Res Commun 107:485–491
Niwa O, Sugahara T (1981) 5-Azacytidine induction of mouse endogenous type C virus and suppression of DNA methylation. Proc Natl Acad Sci USA 78:6290–6294
Nordheim A, Pardue ML, Lafer EM, Muller A, Stoller BD, Rich A (1981) Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes. Nature 294:417–422
Olson CB (1980) 5-Methylcytosine, 5-azacytidine and development: a synthesis. Speculations in science and technology. Elsevier, Sequoia Lausanne
Ostrander M, Vogel S, Silverstein S (1982) Phenotypic switching in cells transformed with the Herpes Simplex virus thymidine kinase gene. Mol Cell Biol 1:708–714
Ott M-O, Sperling L, Cassio D, Levilliers J, Sala-Trepat J, Weiss MC (1982) Undermethylation at the 5′ end of the albumin gene is necessary but not sufficient for albumin production by rat hepatoma cells in culture. Cell 30:825–833
Palmiter RD, Chen HY, Brinster RL (1982) Differential regulation of Metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Cell 29:701–710
Parker MI, Judge K, Gevers W (1982) Loss of type 1 procollagen gene expression in SV40-transformed human fibroblasts is accompanied by hypermethylation of these genes. Nucleic Acids Res 10:5879–5891
Pech M, Streeck RE, Zachau HG (1979) Patchwork structure of a bovine satellite DNA. Cell 18:883–893
Pellicer A, Robins D, Wold B, Sweet R, Jackson J, Lowy I, Roberts JM, Sim GK, Silverstein IS, Axel R (1980) Altering genotype and phenotype by DNA-mediated gene transfer. Science 209:1414–1422
Pollack Y, Stein R, Razin A, Cedar H (1980) Methylation of foreign DNA sequences in eukaryotic cells. Proc Natl Acad Sci USA 77:6463–6467
Pollock JM, Swihard M, Taylor JH (1978) Methylation of DNA in early development: 5-methylcytosine content of DNA in sea urchin sperm and embryos. Nucleic Acids Res 5:4855–4863
Quint A, Cedar H (1981) In vitro methylation of DNA with HpaII methylase. Nucleic Acids Res 9:633–646
Radman M, Villani G, Boiteux S, Kinsella AR, Glickman BW, Spadari S (1979) Replicational fidelity: mechanisms of mutation avoidance and mutation fixation. Cold Spring Harbour Symp Quant Biol 43:937–946
Rae PMM, Steele RE (1978) Modified bases in the DNAs of unicellular eukaryotes: an examination of distributions and possible roles, with emphasis on hydroxy-methyluracil in dinoflagellates. Biosystems 10:37–53
Rae PMM, Steele RE (1979) Absence of cytosine methylation at CCGG and GCGC sites in the rDNA coding regions and intervening sequences of Drosophila and the rDNA of other higher insects. Nucleic Acids Res 6:2987–2995
Rahe B, Erickson RP, Quinto M (1982) DNA methylation during spermatogenesis. J Cell Biol 95:174
Razin A, Cedar H (1977) Distribution of 5-methylcytosine in chromatin. Proc Natl Acad Sci USA 74:2725–2728
Razin A, Urieli S, Pollack T, Gruenbaum Y, Glaser G (1980) Studies on the biological role of DNA methylation; IV. Mode of methylation of DNA in E. coli cells. Nucleic Acids Res 8:1783–1792
Razin A, Riggs AD (1980) DNA methylation and gene function. Science 210:604–610
Razin A, Friedman J, (1981) DNA methylation and its possible biological roles. Prog Nucleic Acid Res Mol Biol 25:33–52
Reilly JG, Braun R, Thomas CA (1980) Methylation in Physarum DNA. FEBS Letts 116:181–184
Reilly JG, Thomas CA, Lundell MJ (1982) Methylation of mouse ribosomal RNA genes. DNA 1:259–266
Riggin CH, Pitha PM (1982) Methylation and a polymorphic restriction site adjacent to human beta-interferon gene. DNA 1:267–271
Riggs AD (1975) X inactivation, differentiation and DNA methylation. Cytogenet Cell Genet 14:9–25
Romanov GA, Vanyushin BF (1981) Methylation of reiterated sequences in mammalian DNAs. Effects of the tissue type, age, malignancy and hormonal induction. Biochim Biophys Acta 653:204–218
Rosen J, Gupta P, Rodgers JR, Yu L, Hobbs AA, Richards DA, Supowit SC (1981) Hormonal regulation of milk protein gene expression. Biochem Soc Trans 9:112
Roy PH, Weissbach A (1975) DNA methylase from HeLa cell nuclei. Nucleic Acids Res 2:1669–1684
Rubery ED, Newton AA (1973) DNA methylation in normal and tumour virus-transformed cells in tissue culture. 1. The level of DNA methylation in BHK21 cells and in BHK21 cells transformed by polyoma virus (Py Y cells). Biochim Biophys Acta 324:24–36
Sager R, Kitchin R (1975) Selective silencing of eukaryotic DNA. Science 189:426–433
Sager R, Grabowy C, Sano H (1981) The mat-1 gene in Chlamydomonas regulates DNA methylation during gametogenesis. Cell 24:41–47
Sager R, Grabowy C, Sano H (1983) Differential methylation of chloroplast DNA regulates maternal inheritance in a methylated mutant of Chlamydomonas. Proc Natl Acad Sci USA 80:3025–3029
Salas CE, Pfohl-Leszkowicz A, Lang MC, Dirheimer G (1979) Effect of modification by N-acetoxy-N-2 acetyl aminofluorene on the level of DNA methylation. Nature 278:71–72
Salomon R, Kaye AM, (1969) Mouse nuclear satellite DNA: 5-Methylcytosine content, pyrimidine isoplith, distribution and electron microscopic appearance. J Mol Biol 43:581–592
Salomon R, Kaye AM (1970) Methylation of mouse DNA in vivo: DI and tripyrimidine sequences containing 5-methylcytosine. Biochim Biophys Acta 204:340–351
Salser W (1978) Globin mRNA sequences: analysis of base pairing and evolutionary implications. Cold Spring Harbour Symp Quant Biol 42:985–1002
Sano H, Sager R (1982) Tissue specificity and clustering of methylated cytosines in bovine satellite I DNA. Proc Natl Acad Sci USA 79:3584–3588
Santi DV, Garrett CE, Barr PJ (1983) On the mechanism of inhibition of DNA-cytosine methyltransferases by cytosine analogs. Cell 33:9–10
Scarano E, Iaccarino M, Grippo P, Parisi E (1967) The heterogeneity of thymine methyl group origin in DNA pyrimidine isostichs of developing sea urchin embryos. Proc Natl Acad Sci USA 57:1394–1400
Schnedl W, Dev VG, Tantravahi R, Miller DA, Erlanger BF, Miller OJ (1975) 5-Methylcytosine in heterochromatic regions of chromosomes: chimpanzee and gorilla compared to the human. Chromosoma 59:59–66
Schneidermann MH, Billen D (1973) Methylation of rapidly reannealing DNA during the cell cycle of Chinese hamster cells. Biochim Biophys Acta 308:352–360
Setlow P (1976) Nearest neighbour frequencies in deoxyribonucleic acids. In: Fasman GD (ed) CRC handbook of biochemistry and molecular biology: Nucleic acids, vol 2, 3rd edn. CRC Press, Cleveland, Ohio
Shapiro HS, Chargaff E (1960) Studies on the nucleotide arrangement in deoxyribonucleic acids. IV. Patterns of nucleotide sequence in the deoxyribonucleic acid of rye germ and its fractions. Biochim Biophys Acta 39:68–82
Shapiro HS (1968) Distribution of purines and pyrimidines in deoxyribonucleic acids. In: CRC handbook of biochemistry. Chemical Rubber Co. Cleveland, Ohio, pp H30–65
Sheffery M, Rifkind RA, Marks PA (1982) Murine erythroleukemia cell differentiation: DNaseI hypersensitivity and DNA methylation near the globin genes. Proc Natl Acad Sci USA 79:1180–1184
Shen CJ, Maniatis T (1980) Tissue specific DNA methylation in a cluster of rabbit β-like globin genes. Proc Natl Acad Sci USA 77:6634–6638
Shmookler-Reis RJ, Goldstein S (1982a) Interclonal variation in methylation patterns for expressed and non-expressed genes. Nucleic Acids Res 10:4293–4304
Shmookler-Reis RJ, Goldstein S (1982b) Variability of DNA methylation patterns during serial passage of human diploid fibroblasts. Proc Natl Acad Sci USA 79:3949–3953
Silber R, Berman E, Goldstein B, Stein H, Farnham G, Bertino JR (1966) Methylation of nucleic acids in normal and leukemic leukocytes. Biochim Biophys Acta 123:638–640
Simon D, Grunert F, Acken UR, Döring HP, Kröger H (1978) DNA-methylase from regenerating rat liver: purification and characterisation. Nucleic Acids Res 6:2153–2167
Sims MA, Doering JL, Hoyle HD (1983) DNA methylation patterns in the 5S DNA's of Xenopus laevis. Nucleic Acids Res 11:277–290
Singer J, Stellwagen RH, Roberts-Ems J, Riggs AD (1977) 5-Methylcytosine content of rat hepatoma DNA substituted with bromodeoxyuridine. J Biol Chem 252:5509–5513
Singer J, Roberts-Ems J, Riggs AD (1979a) Methylation of mouse liver DNA studied by means of restriction enzymes HpaII and MspI. Science 203:1019–1021
Singer J, Roberts-Ems J, Luthardt FW, Riggs AD (1979b) Methylation of DNA in mouse early embryos, teratocarcinoma cells and adult tissues of mouse and rabbit. Nucleic Acids Res 7:2369–2385
Slater MR (1979) Methylation patterns in sea urchin DNA. B.Sc. Honours (Molecular Biology) Thesis, Edinburgh University
Smith SS, Yu JC, Chen CW (1982) Different levels of DNA modification at 5′ CCGG in murine erythroleukemia cells and the tissues of normal mouse spleen. Nucleic Acids Res 10:4305–4320
Sneider TW, Potter VR (1969) Methylation of mammalian DNA: Studies on Novikoff hepatoma cells in tissue culture. J Mol Biol 42:271–284
Sneider TW (1972) Methylation of mammalian deoxyribonucleic acid. III. Terminal versus internal location of 5-methylcytosine in oligodeoxyribonucleotides from Novikoff hepatoma cell deoxyribonucleic acid. J Biol Chem 247:2872–2875
Sneider TW, Teague WM, Rogachevsky LM (1975) S-adenosylmethionine: DNA-cytosine 5-methyltransferase from a Novikoff rat hepatoma line. Nucleic Acids Res 2:1685–1700
Sneider TW (1980) The 5′-cytosine in CCGG is methylated in two eukaryotic DNAs and MspI is sensitive to methylation at this site. Nucleic Acids Res 8:3829–3840
Sneider TW (1981) The importance of DNA methylation. Trends Biochem Sci 6:XI
Sobieski DA, Eden FC (1981) Clustering and methylation of repeated DNA: persistence in avian development and evolution. Nucleic Acids Res 9:6001–6015
Solage A, Cedar H (1978) Organization of 5-methylcytosine in chromosomal DNA. Biochemistry 17:2934–2938
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Stasiak A, Klopotowski T (1979) Four-standed DNA structure and DNA base methylation in the mechanism of action of restriction endonucleases. J Theor Biol 80:65–82
Stein R, Razin A, Cedar H (1982a) In vitro methylation of the hamster adenine phosphoribosyl transferase gene inhibits its expression in mouse L cells. Proc Natl Acad Sci USA 79:3418–3422
Stein R, Gruenbaum Y, Pollack Y, Razin A, Cedar H (1982b) Clonal inheritance of the pattern of DNA methylation in mouse cells. Proc Natl Acad Sci USA 79:61–65
Stein R, Sciaky-Gallili N, Razin A, Cedar H (1983) Pattern of methylation of two genes coding for housekeeping functions. Proc Natl Acad Sci USA 80:2422–2426
Stewart CL, Stuhlmann H, Jahner D, Jaenisch R (1982) De novo methylation, expression and infectivity of retroviral genomes introduced into embryonal carcinoma cells. Proc Natl Acad Sci USA 79:4098–4102
Stuhlmann H, Jähner RD, Jaenisch R (1981) Infectivity and methylation of retroviral genomes is correlated with expression in the animal. Cell 26:221–232
Sturm KS, Taylor JH (1981) Distribution of 5-methylcytosine in DNA of somatic and germline cells from bovine tissues. Nucleic Acids Res 9:4537–4546
Subramanian KN (1982) Effect of in vitro methylation at CpG sites on gene expression in a genome functioning autonomously in a vertebrate host. Nucleic Acids Res 10:3475–3486
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 77:253–256
Szer E, Shugar D (1966) The structure of poly-5-methylcytidylic acid and its twin-stranded complex with polyinosinic acid. J Mol Biol 17:174–187
Tanaka M, Hibasami H, Nagai J, Ikeela T (1980) Effect of 5-azacytidine on DNA methylation in Ehrlichs ascites tumor cells. Aust J Exp Biol Med Sci 58:391–396
Tantravahi U, Breg WR, Wertelecki V, Erlanger BF, Miller OJ (1981a) Evidence for methylation of inactive rRNA genes in amplified regions. Hum Genet 56:315–320
Tantravahi U, Guntaka RV, Erlanger BF, Miller OJ (1981b) Amplified ribosomal RNA genes in a rat hepatoma cell line are enriched in 5-methylcytosine. Proc Natl Acad Sci USA 78:489–493
Taylor JH (1979) Enzymatic methylation of DNA: patterns and possible regulatory roles. In: Molecular genetics, part III, chromosome structure. Academic Press, New York, pp 89–115
Taylor SM, Jones PA (1982) Mechanism of action of eukaryotic methyltransferase. Use of 5-azacytidine containing DNA. J Mol Biol 162:679–692
Tewari KK, Wildman SG (1966) Chloroplast DNA from tobacco leaves. Science 153:1269–1271
Turkington RW, Spielvogel RL (1971) Methylation of deoxyribonucleic acid during hormonal stimulation of mammary cells in vitro. J Biol Chem 246:3835–3840
Turnbull JF, Adams RLP (1976) DNA methylase: purification from ascites cells and the effect of various DNA substrates on its activity. Nucleic Acids Res 3:677–695
Tyler-Smith C (1980) Changes in genome structure and gene expression in methotrexate-resistant mouse cells. PhD Thesis, Edinburgh University
Urieli-Shoval S, Gruenbaum Y, Sedat J, Razin A (1982) The absence of detectable methylated bases in Drosophila melanogaster DNA. FEBS Letts 146:148–152
Van der Ploeg LHT, Flavell RA (1980) DNA methylation in the human γδβ-globin locus in erythroid and nonerythroid tissues. Cell 19:947–958
Van der Ploeg LHT, Groffen J, Flavell RA (1980) A novel type of secondary modification of two CCGG residues in the human γδβ-globin gene locus. Nucleic Acids Res 8:4563–4574
Vanyushin BF, Tkacheva SG, Belozersky AN (1970) Rare bases in animal DNA. Nature 225:948–949
Vanyushin BF, Nemirovsky LE, Klimenko VV, Vasiliev VK, Belozersky AN (1973) The 5-methylcytosine in DNA of rats. Gerontologia 19:138–152
Vanyushin BF, Tushmalova NA, Gus'kova LV, Demidkina NP, Nikandrova LR (1977) Changes in DNA methylation level of rat brain during development of a conditioned reflex. Mol Biol USSR 11:141–146
Vardimon L, Neumann R, Kuhlmann I, Stutter D, Doerfler W (1980) DNA methylation and viral gene expression in adenovirustransformed and-infected cells. Nucleic Acids Res 8:2461–2473
Vardimon L, Kuhlmann I, Doerfler W (1981) Methylation of adenovirus genes in transformed cells and in vitro: influence on the regulation of gene expression. Eur J Cell Biol 25:13–15
Vardimon L, Kressmann A, Cedar H, Maechler M, Doerfler W (1982) Expression of a cloned adnovirus gene is inhibited by in vitro methylation. Proc Natl Acad Sci USA 79:1073–1077
Vasilikaki-Baker H, Nishioka Y (1982) DNA methylation in the Indian Muntjac. J Cell Biol 95:68
Vedel M, Gomez M, Nahon J, Sala-Trepat J (1982), DNA methylation in the rat albumin and alpha-fetoprotein genes: relationship with gene expression. Biol Cell 45:77
Venolia L, Gartler SM, Wassman ER, Yen P, Mohandas T, Shapiro LJ (1982) Transformation with DNA from 5-azacytidine-reactivated X chromosomes. Proc Natl Acad Sci USA 79:2352–2354
Waalwijk C, Flavell RA (1978a) DNA methylation at a CCGG sequence in the large intron of the rabbit β-globin gene: tissue specific variations. Nucleic Acids Res 5:4631–4641
Waalwijk C, Flavell RA (1978b) MspI, an isoschizomer of HpaII which cleaves both unmethylated and methylated HpaII sites. Nucleic Acids Res 5:3231–3236
Wagner R Jr, Meselson M (1976) Repair tracts in mismatched DNA heteroduplexes. Proc Natl Acad Sci USA 73:4135–4139
Wang AH-J, Quigley GJ, Kolpak FJ, Crawford JL, van Boom JH, van der Marel G, Rich A (1979) Molecular structure of a lefthanded double helical DNA fragment at atomic resolution. Nature 282:680–686
Wei L-H, Erlanger BE, Eastman EM, Miller OJ, Goodman R (1981) Inverse relationship between transcriptional activity and 5-methylcytosine content of DNA in polytene chromosomes of Sciara coprophila. Exp Cell Res 135:411–415
Weintraub H, Groudine M (1976) Chromosomal subunits in active genes have an altered conformation. Science 193:848–856
Weintraub H, Larsen A, Groudine M (1981) α-globin gene switching during the development of chicken embryos: expression and chromosome structure. Cell 24:333–344
Weintraub H, Beug H, Groudine M, Graf T (1982) Temperaturesensitive changes in the structure of globin chromatin in lines of red cell precursors transformed by ts-AEV. Cell 28:931–940
Weisbrod S (1982) Active chromatin. Nature 297:289–295
Whittaker PA, Hardman N (1980) Methylation of nuclear DNA in Physarum polycephalum. Biochem J 191:859–862
Whittaker PA, McLachlan A, Hardman N (1981) Sequence organization in nuclear DNA from Physarum polycephalum: methylation of repetitive sequences. Nucleic Acids Res 9:801–814
Wigler M, Levy D, Perucho M, (1981) The somatic replication of DNA methylation. Cell 24:33–40
Wilks AF, Cozens PJ, Mattaj IW, Jost J (1982) Estrogen induces a demethylation at the 5′ end region of the chicken vitellogenin gene. Proc Natl Acad Sci USA 79:4252–4255
Wilson VL, Jones PA (1983) Inhibition of DNA methylation by chemical carcinogens in vitro. Cell 32:239–246
Wolf SF, Migeon BR (1982) Studies of X chromosome DNA methylation in normal human cells. Nature 295:667–671
Wolf SF, Migeon BR (1983) Implications for X-chromosome regulation from studies of human X-chromosome DNA. Cold Spring Harbour Symp Quant Biol 47:621–630
Wyatt GR (1951) Recognition and estimation of 5-methylcytosine in nucleic acids. Biochem J 48:581–584
Yagi M, Koshland ME (1981) Expression of the J chain gene during B cell differentiation is inversely correlated with DNA methylation. Proc Natl Acad Sci USA 78:4907–4911
Youssoufian H, Hamner SA, Hirsch MS, Mulder C (1982) Methylation of the viral genome in an in vitro model of herpes simplex virus latency. Proc Natl Acad Sci USA 79:2207–2210
Zacharias W, Larson JE, Klysik J, Stirdivant SM, Wells RD (1982) Conditions which cause the right-handed to left-handed DNA conformational transitions. Evidence for several types of lefthanded DNA structures in solution. J Biol Chem 257:2775–2782
Zin'kovskaya GG, Berdyshev GD, Vanyushin BF (1979) Tissue-specific decrease and change in nature of DNA methylation in cattle during aging. Biochemistry [New York] 43:1484–1491
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cooper, D.N. Eukaryotic DNA methylation. Hum Genet 64, 315–333 (1983). https://doi.org/10.1007/BF00292363
Issue Date:
DOI: https://doi.org/10.1007/BF00292363