The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its –CH3 served for DNA replication and repair either in bacteria or humans; its entire –CH3 served instead for building N6-methyladenine and 5-methylcytosine on bacterial DNA and 5-methylcytosine alone on human DNA. In humans, although a slight extra-S asymmetric methylation appeared de novo yielding on parental DNA 5’-m5CpC-3’/ 3’-GpG-5’, 5’-m5CpT-3’/3’-GpA-5’ and 5’-m5CpA-3’/3’-GpT-5’ monomethylated dinucleotide pairs, a heavy symmetric methylation involved in S semiconservatively newly made DNA to guarantee genetic maintenance of –CH3 in 5’-m5CpG-3’/3’-Gpm5C-5’ dimethylated dinucleotide pairs. In this framework, an inverse correlation was found between bulk genomic DNA methylation occurring in S and bulk polyA-containing pre-mRNA transcription taking place in G1 and G2. Thus, probes of 1 × 106 Daltons (constructed using sheared by sonication newly made methylated DNA filaments) revealed a modular organization in genes: after the hypermethylated promoter, they exhibited an alternation of unmethylated coding and methylated uncoding sequences. This encouraged the search for a language that genes regulated by methylation should have in common. An initial deciphering of restriction minimaps with hypomethylatable exons vs. hypermethylatable promoters and introns was improved when the bisulfite technique allowed a direct sequencing of m5C. In lymphocytes, where the transglutaminase gene is inactive, its promoter exhibited two fully methylated CpG-rich domains at 5’ and one fully unmethylated CpG-rich domain at 3’, including the site +1 and a 5’-UTR. At variance, in HUVEC cells, where the transglutaminase gene is active, in the first CpG-rich domain of promoter few doublets lost their –CH3. Such an inverse correlation suggested new hypotheses especially in connection with repair-modification: UV radiation would cause demethylation in given loci of a promoter by chance, whilst even a partial demethylation in this promoter would be able to resume a previously silent pre-mRNA transcription.
Scarano, E., Iaccarino, M., Grippo, P. and Winckelmans, D. (1965) On Methylation of DNA during Development of the Sea Urchin Embryo. Journal of Molecular Biology, 14, 603-607. http://dx.doi.org/10.1016/S0022-2836(65)80211-X
Arber, W. (1965) Host Specificity of DNA Produced by Escherichia coli. V. The Role of Methionine in the Production of Host Specificity. Journal of Molecular Biology, 11, 247-256. http://dx.doi.org/10.1016/S0022-2836(65)80055-9
Hattman, S., Brooks, J.E. and Masurekar, M. (1978) Sequence Specificity of the PI Modification Methylase (M?Eco P1) and DNA Methylase (M?Eco dam) Controlled by Escherichia coli dam Gene. Journal of Molecular Biology, 126, 367-380. http://dx.doi.org/10.1016/0022-2836(78)90046-3
Marinus, M.G. and Morris, N.R. (1974) Biological Function for 6-Methyladenine Residues in the DNA of Escherichia coli K12. Journal of Molecular Biology, 85, 309-322. http://dx.doi.org/10.1016/0022-2836(74)90366-0
Raleigh, E.A. and Wilson, G. (1986) Escherichia coli K-12 Restricts DNA-Containing 5-Methylcytosine. Proceedings of the National Academy of Sciences of the United States of America, 83, 9070-9074. http://dx.doi.org/10.1073/pnas.83.23.9070
Raleigh, E.A., Murray, N.E., Revel, H., Blumenthal, R.M., Wastaway, D., Reith, A.D., Rigby, P.W.J., Elhai, J. and Hanahan, D. (1988) McrA and McrB Restriction Phenotypes of Some E. coli Strains and Implications for Gene Cloning. Nucleic Acids Research, 16, 1563-1575. http://dx.doi.org/10.1093/nar/16.4.1563
Gorovsky, M.A., Hattman, S. and Plager, G.L. (1973) [6N]methyl-adenine in the Nuclear DNA of a Eucaryote, Tetrahymena pyriformis. Journal of Cell Biology, 56, 697-701. http://dx.doi.org/10.1083/jcb.56.3.697
Urieli-Shove, S., Gruenbaum, Y., Sedat, J. and Razin, A. (1982) The Absence of Detectable Methylated Bases in Drosophila melanogaster DNA. FEBS Letters, 146, 148-152. http://dx.doi.org/10.1016/0014-5793(82)80723-0
Achwal, C.W., Ganguly, P. and Chandra, H.S. (1984) Estimation of the Amount of 5-Methylcytosine in Drosophila melanogaster DNA by Amplified ELISA and Photoacoustic Spectroscopy. EMBO Journal, 3, 263-266.
Lyko, F., Ramsahoye, B.H., Kashevsky, H., Tudor, M., Mastrangelo, M.A., Orr-Weaver, T.L. and Jaenish, R. (1999) Mammalian (Cytosine-5) Methyltransferases Cause Genomic DNA Methylation and Lethality in Drosophila. Nature Genetics, 23, 363-366. http://dx.doi.org/10.1038/15551
Vanyushin, B.F., Mazin, A.L., Vasilyev, V.K. and Belozersky, A.N. (1973) The Content of 5-Methylcytosine in Animal DNA: The Species and Tissue Specificity. Biochimica et Biophysica Acta, 299, 397-403. http://dx.doi.org/10.1016/0005-2787(73)90264-5
Vanyushin, B.F., Nemirovsky, L.E., Klimenko, V.V., Vasilyev, V.K. and Belozersky, A.N. (1973) The 5-Methylcytosine in DNA of Rats: Tissue and Age Specificity and the Changes Induced by Hydrocortisone and Other Agents. Gerontology, 19, 138-152. http://dx.doi.org/10.1159/000211967
Volpe, P. and Giuditta, A. (1967) Studies on an Unknown Compound from Ox Brain: II. Separation into Several Components. Journal of Neurochemistry, 14, 637-647. http://dx.doi.org/10.1111/j.1471-4159.1967.tb09567.x
Eremenko, T., Benedetto, A. and Volpe, P. (1972) Virus Infection as a Function of the Host Cell Cycle: Replication of Poliovirus RNA. Journal of General Virology, 16, 61-68. http://dx.doi.org/10.1099/0022-1317-16-1-61
Volpe, P. and Strecker, H.J. (1968) Amphi-Directional Control of a Reversible Reaction Common to Two Enzyme Sequences. Biochemical and Biophysical Research Communications, 32, 240-245. http://dx.doi.org/10.1016/0006-291X(68)90375-6
Volpe, P. and Eremenko, T. (1971) Biochemical Differentiation and Cancerogenesis. In: Neskovic, B., Ed., Proceedings of the International Symposium on Experimental Oncology, Ognjon Prica Publishers, Zagreb, 200-203.
Volpe, P., Menna, T. and Pagano, G. (1974) Ornithine-Delta-Transaminase Heterogeneity and Regulation: Sequential Expression of the “Liver” and “Kidney” Enzyme Forms during the HeLa Cell Cycle. European Journal of Biochemistry, 44, 455-458. http://dx.doi.org/10.1111/j.1432-1033.1974.tb03503.x
Geraci, D., Eremenko, T., Cocchiara, R., Granieri, A., Scarano, E. and Volpe, P. (1974) Correlation between Synthesis and Methylation of DNA in HeLa Cells. Biochemical and Biophysical Research Communications, 57, 353-361. http://dx.doi.org/10.1016/0006-291X(74)90937-1
Duranti, T., La Teana, A., Cacciamani, T. and Volpe, P. (2006) The Prokaryotic Origin of the Pathways for Synthesis and Post-Synthetic Modification of DNA. RNA Biology, 3, 49-53. http://dx.doi.org/10.4161/rna.3.1.2794
Eremenko, T., Palitti, F., Morelli, F., Whitehead, E.P. and Volpe, P. (1985) Hypomethylation of Repair Patches in HeLa Cells. Molecular Biology Reports. 10, 177-182. http://dx.doi.org/10.1007/BF00778526
Feng, T.Y. and Chang, K.S. (1984) Persistence of Maternal Inheritance in Chlamydomonas Despite Hypomethylation of Chloroplast DNA Induced by Inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 81, 3438-3442. http://dx.doi.org/10.1073/pnas.81.11.3438
Franchina, M., Hooper, J. and Kay, P.H. (2001) Five Novel Alternatively Spliced Transcripts of DNA (Cytosine-5) Methyltransferase 2 in Human Peripheral Blood Leukocytes. International Journal of Biochemistry and Cell Biology, 33, 1104-1115. http://dx.doi.org/10.1016/S1357-2725(01)00074-7
Scarano, E., Iaccarino, M., Grippo, P. and Parisi, E. (1967) Heterogeneity of Thymine Methyl Group Origin in DNA Pyrimidine Isostichs of Developing Sea Urchin Embryos. Proceedings of the National Academy of Sciences of the United States of America, 57, 1394-1400. http://dx.doi.org/10.1073/pnas.57.5.1394
Bestor, T.H. and Ingram, V.M. (1983) Two Species of DNA Methyltransferase from Murine Erythroleukemia Cells: Purification, Sequence Specificity, and Mode of Interaction with DNA. Proceedings of the National Academy of Sciences of the United States of America, 80, 5559-5563. http://dx.doi.org/10.1073/pnas.80.18.5559
Delfini, C., Crema, A.L., Alfani, E., Lo Presti, E., Eremenko, T. and Volpe, P. (1987) DNA-Methylases Separated through the HeLa Cell Cycle Methodology Show Allosteric Properties. FEBS Letters, 210, 17-21.
Eremenko, T., Delfini, C., Crema, A.L., Alfani, E. and Volpe, P. (1988) Uncoupling of the DNA Polymerase and Methylase Systems Leads to Hypomethylation of Repair Patches. Macromolecules in the Functioning Cell, 5, 37-41.
Volpe, P. and Eremenko, T. (1970) A Method to Measure the Length of Each Phase of the Cell Cycle in Spinner Cultures. Experimental Cell Research, 60, 456-458. http://dx.doi.org/10.1016/0014-4827(70)90542-2
Evans, H.H., Evans, T.E. and Littman, S. (1973) Methylation of Parental and Progeny DNA Strands in Physarum polycephalum. Journal of Molecular Biology, 74, 563-574. http://dx.doi.org/10.1016/0022-2836(73)90047-8
Bird, A.P. (1978) Use of Restriction Enzymes to Study Eucaryotic DNA Methylation: The Symmetry of Methylated Sites Supports Semi-Conservative Copying of the Methylation Pattern. Journal of Molecular Biology, 118, 49-60. http://dx.doi.org/10.1016/0022-2836(78)90243-7
Penman, S., Vesco, C. and Penman, M. (1968) Localization and Kinetics of Formation of Nuclear Heterodisperse RNA, Cytoplasmic Heterodisperse RNA and Polyribosome Associated Messenger RNA in HeLa Cells. Journal of Molecular Biology, 34, 49-62. http://dx.doi.org/10.1016/0022-2836(68)90234-9
Georgyev, G.P. (1969) On the Structural Organization of Operon and on the Regulation of RNA Synthesis in Animal Cells. Journal of Theoretical Biology, 25, 227-231. http://dx.doi.org/10.1016/S0022-5193(69)80034-2
Brack, C. and Tonegawa, S. (1977) Variable and Constant Parts of the Immunoglobulin Light Chain Gene of a Mouse Myeloma Cell Are 1250 Nontranslated Bases Apart. Proceedings of the National Academy of Sciences of the United States of America, 74, 5652-5656. http://dx.doi.org/10.1073/pnas.74.12.5652
Doel, M.T., Houghton, M., Cook, E.A. and Carey, N.H. (1977) The Presence of Ovalbumin mRNA Coding Sequences in Multiple Restriction Fragments of Chicken DNA. Nucleic Acids Research, 4, 3701-3713. http://dx.doi.org/10.1093/nar/4.11.3701
Berget, S.M., Moore, C. and Sharp, P.A. (1977) Spliced Segments at the 5’ Terminus of Adenovirus 2 Late mRNA. Proceedings of the National Academy of Sciences of the United States of America, 74, 3171-3175. http://dx.doi.org/10.1073/pnas.74.8.3171
Tilghman, S.M., Tiemeier, D.C., Seldman, J.G., Peterlin, B.M., Sullivan, M., Maizel, J.V. and Leder, P. (1978) Intervening Sequence of DNA Identified in the Structural Portion of a Mouse Beta-Globin Gene. Proceedings of the National Academy of Sciences of the United States of America, 75, 725-729. http://dx.doi.org/10.1073/pnas.75.2.725
Tentravahi, V., Guntaka, R.V., Erlanger, B.F. and Miller, O.J. (1981) Amplified Ribosomal RNA Genes in a Rat Hepathoma Cell Line Are Enriched in 5-Methylcytosine. Proceedings of the National Academy of Sciences of the United States of America, 78, 489-493. http://dx.doi.org/10.1073/pnas.78.1.489
Eremenko, T., Esposito, C., Iacovacci, P., Benedetto, A., Elia, G., Delfini, C., Alfani, E., Cascio, O., Sarpietro, M.G., Fazzio, A. and Volpe, P. (1990) Is 5-Methylcytosine a Regulatory Signal in Eukaryotic Gene Expression? 7th International Symposium on Macromolecules in the Functioning Cell, Taormina, Abstracts, 22.
Volpe, P., Esposito, C., Iacovacci, P., Butler, R.H. and Eremenko, T. (1993) Language of Genes with Inverse Correlation between Methylation and Transcription. Macromolecules in the Functioning Cell, 7, 59-71.
Volpe, P. and Eremenko, T. (1973) Nuclear and Cytoplasmic DNA Synthesis during the Mitotic Cycle of HeLa Cells. European Journal of Biochemistry, 32, 227-232. http://dx.doi.org/10.1111/j.1432-1033.1973.tb02600.x
Volpe, P., Granieri, A. and Eremenko, T. (1975) Negli eucarioti i geni si metilano ordinatamente durante la replica. 12th Meeting of the Italian Society of Biophysics and Molecular Biology, Pavia, Abstracts, 49.
Eremenko, T., Granieri, A. and Volpe, P. (1978) Organization, Replication and Modification of the Human Genome: I. Differential Methylation of Two Classes of HeLa Nuclear DNA Separated on Ag+/Cs2SO4 Gradients. Molecular Biology Reports, 4, 163-170. http://dx.doi.org/10.1007/BF00777518
Eremenko, T., Granieri, A. and Volpe, P. (1978) Organization, Replication and Modification of the Human Genome: II. Temporal Order of Synthesis and Methylation of Two Classes of HeLa nDNA Separated in Ag+/Cs2SO4 Gradients. Molecular Biology Reports, 4, 237-240. http://dx.doi.org/10.1007/BF00777561
Eremenko, T., Timofeeva, M.Y. and Volpe, P. (1980) Organization, Replication and Modification of the Human Genome: Synthesis and Methylation of Palindromic, Repeated and Unique Hela nDNA Sequences during the S-Phase. Molecular Biology Reports, 6, 131-136. http://dx.doi.org/10.1007/BF00775405
Delfini, C., Alfani, E., De Venezia, V., Oberholtzer, G., Tomasello, C., Eremenko, T. and Volpe, P. (1985) Cell-Cycle Dependence and Properties of the HeLa Cell DNA Polymerase System. Proceedings of the National Academy of Sciences of the United States of America, 82, 2220-2224. http://dx.doi.org/10.1073/pnas.82.8.2220
Kruger, D., Schroeder, C., Reuter, M., Bogdarina, I., Buryanov, Y. and Bickle, T. (1985) DNA Methylation of Bacterial Viruses T3 and T7 by Different DNA Methylases in Escherichia coli K12 Cells. European Journal of Biochemistry, 150, 323-330. http://dx.doi.org/10.1111/j.1432-1033.1985.tb09024.x
Mandel, J.L. and Chambon, P. (1979) DNA Methylation: Organ Specific Variations in the Methylation Pattern within and Oround Ovalbumin and Other Chicken Genes. Nucleic Acids Research, 7, 2081-2092. http://dx.doi.org/10.1093/nar/7.8.2081
Sutter, D. and Doerfler, W. (1980) Methylation of Integrated Adenovirus Type 12 DNA Sequences in Trasformed Cells Is Inversely Correlated with Viral Gene Expression. Proceedings of the National Academy of Sciences of the United States of America, 77, 253-256. http://dx.doi.org/10.1073/pnas.77.1.253
Liau, M.C., Chang, C.F., Saunders, G.F. and Tsai, Y.H. (1981) S-Adenosylhomocysteine Hydrolases as the Primary Target Enzymes in Androgen Regulation of Methylated Complexes. Archives of Biochemistry and Biophysics, 208, 261-272. http://dx.doi.org/10.1016/0003-9861(81)90148-X
Geraci, D., Eremenko, T., Granieri, A., Scarano, E. and Volpe, P. (1973) The in Vivo and in Vitro Methylation of DNA in Synchronized HeLa Cells. 9th International Congress of Biochemistry, Stockholm, Abstracts, 3m64, 190.
Grippo, P., Iaccarino, M., Parisi, E. and Scarano, E. (1968) Methylation of DNA in Developing Sea Urchin Embryos. Journal of Molecular Biology, 36, 195-208. http://dx.doi.org/10.1016/0022-2836(68)90375-6
Augusti-Tocco, G., Carestia, C., Grippo, P., Parisi, E. and Scarano, E. (1968) Thin-Layer Electrophoresis of Nucleic Acid Derivatives on Microcrystalline Cellulose. Biochimca et Biophysica Acta, 155, 8-18. http://dx.doi.org/10.1016/0005-2787(68)90329-8
Lu, S., Saydak, M., Gentile, V., Steins, J.P. and Davies, J.A. (1995) Isolation and Characterization of the Human Tissue Transglutaminase Gene Promoter. Journal of Biological Chemistry, 270, 9748-9756. http://dx.doi.org/10.1074/jbc.270.17.9748
Frommer, M., McDonald, L.E., Millar, D.S., Collins, C., Watt, F., Grigg, G.W., Molloy, P.L. and Paul, C.L. (1992) A Genomic Sequencing Protocol That Yields a Positive Display of 5-Methylcytosine Residues in Individual DNA Strands. Proceedings of the National Academy of Sciences of the United States of America, 89, 1827-1831. http://dx.doi.org/10.1073/pnas.89.5.1827
Lu, S. and Davies, P.J.A. (1997) Regulation of the Expression of the Tissue Transglutaminase Gene by DNA Methylation. Proceedings of the National Academy of Sciences of the United States of America, 94, 4692-4697. http://dx.doi.org/10.1073/pnas.94.9.4692
Cacciamani, T., Virgili, S., Centurelli, M., Bertoli, E., Eremenko, T. and Volpe, P. (2002) Specific Methylation of the CpG-Rich Domains in the Promoter of the Human Tissue Transglutaminase Gene. Gene, 297, 103-112. http://dx.doi.org/10.1016/S0378-1119(02)00874-0
Razin, A. and Cedar, H. (1977) Distribution of 5-Methylcytosine in Chromatin. Proceedings of the National Academy of Sciences of the United States of America, 74, 2725-2728. http://dx.doi.org/10.1073/pnas.74.7.2725
Meehan, R., Antequera, F., Lewis, J., McLeod, D., McKay, S., Kleiner, E. and Bird, A.P. (1990) A Nuclear Protein That Binds Preferentially to Methylated DNA in Vitro May Play a Role in the Inaccessibility of Methylated CpGs in Mammalian Nuclei. Philosophical Transactions of the Royal Society of London, B326, 199-205. http://dx.doi.org/10.1098/rstb.1990.0004
Wade, P.A., Gegonne, A., Jones, P.L., Ballestar, E., Aubry, F. and Wolffe, A.P. (1999) Mi-2 Complex Couples DNA Methylation to Chromatin Remodelling and Histone Deacetylation. Nature Genetics, 23, 62-66. http://dx.doi.org/10.1038/12664
Volpe, P., Parasassi, T., Sapora, O., Ravagnan, G. and Eremenko, T. (1999) Influence of the Low Doses of Radiation on the DNA Double Helix, Gene Expression and Membranal State. International Journal of Radiation Medicine, 1, 78-89.
Volpe, P. (1996) Dall’origine del codice all’evoluzione del gene eucariotico (Lectio Doctoralis in Occasion of the Laurea Honoris Causa in Biological Sciences with Biotechnological Specialization). Università degli Studi, Ancona, 1-35.
Kruger, D.H., Shroeder, C., Reuter, M., Bogdarina, I.G., Buryanov, Y.I. and Bickle, T.A. (1985) DNA Methylation of Bacterial Viruses T3 and T7 by Different DNA Methylases in Escherichia coli K12 Cells. European Journal of Biochemistry, 150, 323-330. http://dx.doi.org/10.1111/j.1432-1033.1985.tb09024.x
Gorelick, R. (2003) Transposable Elements Suppress Recombination in All Meiotic Eukaryotes, Including Automictic Ancient Asexuals: A Reply to Schon and Martens. Journal of Natural History, 37, 903-909. http://dx.doi.org/10.1080/0022293021000007705
Lingua, G., Trotta, A., Prigione, V., Ugoccioni, R. and Berta, G. (2005) Nucleus Size in the Host Cells of an Arbuscular Mycorrhizal System: A Mathematical Approach to Estimate the Role of Ploidy and Chromatin Condensation. Karyologia, 58, 112-121.
Zemskov, E.A., Janiak, A., Hang, J., Waghray, A. and Belkin, A.M. (2006) The Role of Tissue Transglutaminase in Cell-Matrix Interactions. Frontiers in Bioscience, 11, 1057-1076. http://dx.doi.org/10.2741/1863
Lai, T.S., Liu, Y., Li, W. and Greenberg, C.S. (2007) Identification of Two GTP-Independent Alternatively Spliced Forms of Tissue Transglutaminase in Human Leukocytes, Vascular Smooth Muscle,and Endothelial Cells. FASEB Journal, 21, 4131-4143. http://dx.doi.org/10.1096/fj.06-7598com
Malousi, A., Maglaveras, N. and Kouidou, S. (2008) Intronic CpG Content and Alternative Splicing in Human Genes Containing a Single Cassette Exon. Epigenetics, 3, 69-73. http://dx.doi.org/10.4161/epi.3.2.6066
Lukasik, M., Karmalska, J., Szutowski, M.M. and Lukaszkiewicz, J. (2009) Wplyw metylacji DNA na funkcjonowanie genomu. Biuletyn Wydzialu Farmaceutycznego Warszawskiego Uniwersytetu Medycznego, 2, 13-18.