N6-Methyladenine: A Conserved and Dynamic DNA Mark.

Chromatin, consisting of deoxyribonucleic acid (DNA) wrapped around histone proteins, facilitates DNA compaction and allows identical DNA codes to confer many different cellular phenotypes. This biological versatility is accomplished in large part by posttranslational modifications to histones and chemical modifications to DNA. These modifications direct the cellular machinery to expand or compact specific chromatin regions and mark regions of the DNA as important for cellular functions. While each of the four bases that make up DNA can be modified (Iyer et al. 2011), this chapter will focus on methylation of the sixth position on adenines (6mA), as this modification has been poorly characterized in recently evolved eukaryotes, but shows promise as a new conserved layer of epigenetic regulation. 6mA was previously thought to be restricted to unicellular organisms, but recent work has revealed its presence in metazoa. Here, we will briefly describe the history of 6mA, examine its evolutionary conservation, and evaluate the current methods for detecting 6mA. We will discuss the enzymes that bind and regulate this mark and finally examine known and potential functions of 6mA in eukaryotes.

[1]  Wei Wang,et al.  A histone methylation network regulates transgenerational epigenetic memory in C. elegans. , 2014, Cell reports.

[2]  J. Rogers,et al.  Comparison of the effects of N6-methyldeoxyadenosine and N5-methyldeoxycytosine on transcription from nuclear gene promoters in barley. , 1995, The Plant journal : for cell and molecular biology.

[3]  Zhike Lu,et al.  m6A-dependent regulation of messenger RNA stability , 2013, Nature.

[4]  P. Borst,et al.  Hypermodified bases in DNA , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  J. Casadesús,et al.  Epigenetic Gene Regulation in the Bacterial World , 2006, Microbiology and Molecular Biology Reviews.

[6]  K. Skarstad,et al.  E. coli SeqA protein binds oriC in two different methyl-modulated reactions appropriate to its roles in DNA replication initiation and origin sequestration , 1995, Cell.

[7]  Bifeng Yuan,et al.  Determination of DNA adenine methylation in genomes of mammals and plants by liquid chromatography/mass spectrometry , 2015 .

[8]  D. B. Dunn,et al.  The occurrence of 6-methylaminopurine in deoxyribonucleic acids. , 1958, The Biochemical journal.

[9]  Albert Jeltsch,et al.  Transition from Nonspecific to Specific DNA Interactions along the Substrate-Recognition Pathway of Dam Methyltransferase , 2005, Cell.

[10]  D. Santi,et al.  On the mechanism of DNA-adenine methylase. , 1988, The Journal of biological chemistry.

[11]  F. Tronche,et al.  The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation , 1989, Molecular and cellular biology.

[12]  M. Meselson,et al.  DNA Restriction Enzyme from E. coli , 1968, Nature.

[13]  R. Wolfenden,et al.  1-Methyladenosine. Dimroth rearrangement and reversible reduction. , 1968, Biochemistry.

[14]  M. Ehrlich,et al.  Tissue-specific differences in DNA methylation in various mammals. , 1983, Biochimica et biophysica acta.

[15]  Lucy Shapiro,et al.  A DNA methylation ratchet governs progression through a bacterial cell cycle , 2007, Proceedings of the National Academy of Sciences.

[16]  D. Wion,et al.  N6-methyl-adenine: an epigenetic signal for DNA–protein interactions , 2006, Nature Reviews Microbiology.

[17]  P. Bates,et al.  Repair of alkylated DNA: recent advances. , 2007, DNA repair.

[18]  Shunmin He,et al.  N6-Methyladenine DNA Modification in Drosophila , 2015, Cell.

[19]  J. M. Goddard,et al.  Methylated bases in DNA from Paramecium aurelia. , 1974, Biochimica et biophysica acta.

[20]  P. Rae,et al.  Macronuclear DNA of the hypotrichous ciliate Oxytricha fallax. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[21]  W. Reik,et al.  The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells , 2012, Molecular cell.

[22]  B. Vanyushin,et al.  Rare Bases in Animal DNA , 1970, Nature.

[23]  P. V. von Hippel,et al.  D(M6ATP) as a probe of the fidelity of base incorporation into polynucleotides by Escherichia coli DNA polymerase I. , 1978, The Journal of biological chemistry.

[24]  B. Glickman Spontaneous mutagenesis in Escherichia coli strains lacking 6-methyladenine residues in their DNA: an altered mutational spectrum in dam- mutants. , 1979, Mutation research.

[25]  Yi Xing,et al.  m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. , 2014, Cell stem cell.

[26]  Xiaodong Cheng,et al.  Structure and substrate recognition of the Escherichia coli DNA adenine methyltransferase. , 2006, Journal of molecular biology.

[27]  Chengqi Yi,et al.  N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO , 2011, Nature chemical biology.

[28]  Nancy Kleckner,et al.  SeqA: A negative modulator of replication initiation in E. coli , 1994, Cell.

[29]  M. Kupiec,et al.  Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq , 2012, Nature.

[30]  I. Henderson,et al.  The SRA Methyl-Cytosine-Binding Domain Links DNA and Histone Methylation , 2007, Current Biology.

[31]  N. Reich,et al.  Kinetic mechanism of the EcoRI DNA methyltransferase. , 1991, Biochemistry.

[32]  R. Katakura,et al.  Methylated cytosine level in human liver DNA does not decline in aging process , 1992, Mechanisms of Ageing and Development.

[33]  N. Murray 2001 Fred Griffith review lecture. Immigration control of DNA in bacteria: self versus non-self. , 2002, Microbiology.

[34]  L. Shapiro,et al.  A cell cycle-regulated bacterial DNA methyltransferase is essential for viability. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[35]  W. Szybalski,et al.  A simple method for locating methylated bases in DNA using class-IIS restriction enzymes. , 1988, Gene.

[36]  N. Lopatina,et al.  The host specificity system inEscherichia coli SK , 1976, Molecular and Cellular Biochemistry.

[37]  Marc Pignot,et al.  Structure of the N6-adenine DNA methyltransferase M•TaqI in complex with DNA and a cofactor analog , 2001, Nature Structural Biology.

[38]  W. G. Kelly,et al.  A C. elegans LSD1 Demethylase Contributes to Germline Immortality by Reprogramming Epigenetic Memory , 2009, Cell.

[39]  J. V. Van Etten,et al.  DNA methylation of viruses infecting a eukaryotic Chlorella-like green alga. , 1985, Nucleic acids research.

[40]  H Yamaki,et al.  The oriC unwinding by dam methylation in Escherichia coli. , 1988, Nucleic acids research.

[41]  A. Krais,et al.  Genomic N6‐methyladenine determination by MEKC with LIF , 2010, Electrophoresis.

[42]  A. Razin,et al.  Clonal inheritance of the pattern of DNA methylation in mouse cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[43]  P. Rae Hydroxymethyluracil in eukaryote DNA: a natural feature of the pyrrophyta (dinoflagellates). , 1976, Science.

[44]  David R. Liu,et al.  Conversion of 5-Methylcytosine to 5- Hydroxymethylcytosine in Mammalian DNA by the MLL Partner TET1 , 2009 .

[45]  C. Timpte,et al.  Induction of sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene. , 2002, Nucleic acids research.

[46]  T. Ramakrishnan,et al.  Deoxyribonucleic acid methylation in mycobacteria , 1981, Journal of bacteriology.

[47]  Tyson A. Clark,et al.  Direct detection of DNA methylation during single-molecule, real-time sequencing , 2010, Nature Methods.

[48]  R. Ghirlando,et al.  Insights into negative modulation of E. coli replication initiation from the structure of SeqA–hemimethylated DNA complex , 2002, Nature Structural Biology.

[49]  J. Davie,et al.  5-Methylcytosine is not detectable in Saccharomyces cerevisiae DNA , 1984, Molecular and cellular biology.

[50]  D. Low,et al.  Roles of DNA Adenine Methylation in Regulating Bacterial Gene Expression and Virulence , 2001, Infection and Immunity.

[51]  C. Dohno,et al.  Discrimination of N6-methyl adenine in a specific DNA sequence. , 2010, Chemical communications.

[52]  A. Abeles,et al.  A protein that binds to the P1 origin core and the oriC 13mer region in a methylation‐specific fashion is the product of the host seqA gene. , 1995, The EMBO journal.

[53]  Tyson A. Clark,et al.  Global methylation state at base-pair resolution of the Caulobacter genome throughout the cell cycle , 2013, Proceedings of the National Academy of Sciences.

[54]  Chuan He,et al.  RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation , 2015, Genes & development.

[55]  Michael G. Cornelius,et al.  Total nucleotide analysis of Hydra DNA and RNA by MEKC with LIF detection and 32P‐postlabeling , 2010, Electrophoresis.

[56]  M. Rogers,et al.  Isolation of mutants sensitive to 2-amiriopurine and alkylating agents and evidence for the role of DNA methylation in Penicillium chrysogenum , 2004, Current Genetics.

[57]  S. Hattman,et al.  Comparative study of DNA methylation in three unicellular eucaryotes , 1978, Journal of bacteriology.

[58]  Michael McClelland Selection againstdam methylation sites in the genomes of DNA of enterobacteriophages , 1985, Journal of Molecular Evolution.

[59]  S. Luria,et al.  A NONHEREDITARY, HOST-INDUCED VARIATION OF BACTERIAL VIRUSES , 1952, Journal of bacteriology.

[60]  P. Modrich,et al.  Requirement for d(GATC) sequences in Escherichia coli mutHLS mismatch correction. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[61]  J. Zelinka,et al.  Modification methylase M.Sau3239I from Streptomyces aureofaciens 3239 , 1990, FEBS letters.

[62]  E. Koonin,et al.  Viral AlkB proteins repair RNA damage by oxidative demethylation , 2008, Nucleic acids research.

[63]  S. Zhong,et al.  Adenosine Methylation in Arabidopsis mRNA is Associated with the 3′ End and Reduced Levels Cause Developmental Defects , 2012, Front. Plant Sci..

[64]  K. Karrer,et al.  Methylation of adenine in the nuclear DNA of Tetrahymena is internucleosomal and independent of histone H1. , 2002, Nucleic acids research.

[65]  Kristina M Smith,et al.  Genome-wide high throughput analysis of DNA methylation in eukaryotes. , 2009, Methods.

[66]  Chuan He,et al.  High-Resolution Mapping of N⁶-Methyladenosine in Transcriptome and Genome Using a Photo-Crosslinking-Assisted Strategy. , 2015, Methods in enzymology.

[67]  J. Josse,et al.  ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID. INFLUENCE OF BACTERIOPHAGE T2 ON THE SYNTHETIC PATHWAY IN HOST CELLS. , 1959, Proceedings of the National Academy of Sciences of the United States of America.

[68]  M. Marinus,et al.  Analysis of Global Gene Expression and Double-Strand-Break Formation in DNA Adenine Methyltransferase- and Mismatch Repair-Deficient Escherichia coli , 2005, Journal of bacteriology.

[69]  E. Greer,et al.  Mutation of C. elegans demethylase spr-5 extends transgenerational longevity , 2015, Cell Research.

[70]  M. Schaechter,et al.  SeqA limits DnaA activity in replication from oriC in Escherichia coli , 1994, Molecular microbiology.

[71]  Charles R. Bradshaw,et al.  Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications , 2015, Nature Structural &Molecular Biology.

[72]  Chris P. Ponting,et al.  The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase , 2007, Science.

[73]  Pre-steady state kinetics of bacteriophage T4 dam DNA-[N(6)-adenine] methyltransferase: interaction with native (GATC) or modified sites. , 2000, Nucleic acids research.

[74]  J. Rabinowitz,et al.  Biosynthesis of ribothymidine in the transfer RNA of Streptococcus faecalis and Bacillus subtilis. A methylation of RNA involving 5,10-methylenetetrahydrofolate. , 1976, The Journal of biological chemistry.

[75]  S. Mason Purine studies. Part II. The ultra-violet absorption spectra of some mono- and poly-substituted purines , 1954 .

[76]  H. Myllykallio,et al.  Identification of a novel gene encoding a flavin-dependent tRNA:m5U methyltransferase in bacteria—evolutionary implications , 2005, Nucleic acids research.

[77]  W. Lam,et al.  Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells , 2005, Nature Genetics.

[78]  D. Santi,et al.  Kinetic and catalytic mechanism of HhaI methyltransferase. , 1987, The Journal of biological chemistry.

[79]  H. Chandra,et al.  Immunochemical evidence for the presence of 5mC, 6mA and 7mG in human, Drosophila and mealybug DNA , 1983, FEBS letters.

[80]  T. B. Johnson,et al.  RESEARCHES ON PYRIMIDINES. C111. THE DISCOVERY OF 5-METHYL-CYTOSINE IN TUBERCULINIC ACID, THE NUCLEIC ACID OF THE TUBERCLE BACILLUS1 , 1925 .

[81]  N. Kleckner,et al.  IS10 transposition is regulated by DNA adenine methylation , 1985, Cell.

[82]  K. Skarstad,et al.  Effects of purified SeqA protein on oriC‐dependent DNA replication in vitro , 1998, The EMBO journal.

[83]  J. Bender,et al.  An Arabidopsis SET domain protein required for maintenance but not establishment of DNA methylation , 2002, The EMBO journal.

[84]  Shu-Bing Qian,et al.  Dynamic m6A mRNA methylation directs translational control of heat shock response , 2015, Nature.

[85]  S. Hattman,et al.  Nucleosome phasing in Tetrahymena macronuclei. , 1983, The Journal of protozoology.

[86]  R. Jaenisch,et al.  Development: DNA methylation in Drosophila melanogaster , 2000, Nature.

[87]  M. Ehrlich,et al.  DNA methylation in thermophilic bacteria: N4-methylcytosine, 5-methylcytosine, and N6-methyladenine. , 1985, Nucleic acids research.

[88]  W. Mages,et al.  A link between DNA methylation and epigenetic silencing in transgenic Volvox carteri. , 2001, Nucleic acids research.

[89]  O. Nureki,et al.  Structural and biochemical analyses of hemimethylated DNA binding by the SeqA protein. , 2004, Nucleic acids research.

[90]  Harry Venner,et al.  Nachweis von Minoritätsbasen in Sperma-Desoxyribonucleinsäure , 1966 .

[91]  P. Borst,et al.  β-d-glucosyl-hydroxymethyluracil: A novel modified base present in the DNA of the parasitic protozoan T. brucei , 1993, Cell.

[92]  Xin Deng,et al.  Widespread occurrence of N6-methyladenosine in bacterial mRNA , 2015, Nucleic acids research.

[93]  R K Gordon,et al.  S‐Adenosylmetliionine and methylation , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[94]  James A. Swenberg,et al.  DNA methylation on N6-adenine in mammalian embryonic stem cells , 2016, Nature.

[95]  I. Capesius,et al.  Determination of 5-methylcytosine from plant DNA by high-performance liquid chromatography. , 1981, Biochimica et biophysica acta.

[96]  A. Granoff,et al.  Frog virus 3 DNA is heavily methylated at CpG sequences. , 1980, Virology.

[97]  Magnar Bjørås,et al.  Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA , 2003, Nature.

[98]  P. Hagerman,et al.  Origin of the intrinsic rigidity of DNA. , 2004, Nucleic acids research.

[99]  K. Carter,et al.  Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair. , 1996, Nucleic acids research.

[100]  A. Kornberg,et al.  Glucosylation of deoxyribonucleic acid by enzymes from bacteriophage-infected Escherichia coli. , 1961, The Journal of biological chemistry.

[101]  G Bernardi,et al.  Evolutionary changes in CpG and methylation levels in the genome of vertebrates. , 1997, Gene.

[102]  Daniel J. G. Lahr,et al.  Estimating the timing of early eukaryotic diversification with multigene molecular clocks , 2011, Proceedings of the National Academy of Sciences.

[103]  Jonas Korlach,et al.  DNA Methylation Assessed by SMRT Sequencing Is Linked to Mutations in Neisseria meningitidis Isolates , 2015, PloS one.

[104]  N. Morris,et al.  Deoxyribonucleic Acid Methylation and Development in Caulobacter bacteroides , 1973, Journal of bacteriology.

[105]  L. Doré,et al.  N 6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas , 2015, Cell.

[106]  T. Kakutani,et al.  Meiotically and mitotically stable inheritance of DNA hypomethylation induced by ddm1 mutation of Arabidopsis thaliana. , 1999, Genetics.

[107]  R. Teoule,et al.  A two-dimensional 1H-NMR study of the dam methylase site: comparison between the hemimethylated GATC sequence, its unmethylated analogue and a hemimethylated CATG sequence. The sequence dependence of methylation upon base-pair lifetimes. , 1987, European journal of biochemistry.

[108]  T. Bestor,et al.  The DNA methyltransferases of mammals. , 2000, Human molecular genetics.

[109]  M. Marinus,et al.  Isolation of Deoxyribonucleic Acid Methylase Mutants of Escherichia coli K-12 , 1973, Journal of bacteriology.

[110]  L. Shapiro,et al.  A cell cycle-regulated adenine DNA methyltransferase from Caulobacter crescentus processively methylates GANTC sites on hemimethylated DNA. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[111]  R. Teoule,et al.  Consequences of methylation on the amino group of adenine. A proton two-dimensional NMR study of d(GGATATCC) and d(GGm6ATATCC). , 1985, European journal of biochemistry.

[112]  Peter A. Jones Functions of DNA methylation: islands, start sites, gene bodies and beyond , 2012, Nature Reviews Genetics.

[113]  D. Lilley,et al.  Base methylation and local DNA helix stability. Effect on the kinetics of cruciform extrusion. , 1989, Journal of molecular biology.

[114]  R. Myers,et al.  Alterations in DNA helix stability due to base modifications can be evaluated using denaturing gradient gel electrophoresis. , 1987, Journal of molecular biology.

[115]  Chun-Xiao Song,et al.  Mechanism and function of oxidative reversal of DNA and RNA methylation. , 2014, Annual review of biochemistry.

[116]  Chuan He,et al.  N 6 -methyladenosine Modulates Messenger RNA Translation Efficiency , 2015, Cell.

[117]  M. Valvano,et al.  Dam Methylation Participates in the Regulation of PmrA/PmrB and RcsC/RcsD/RcsB Two Component Regulatory Systems in Salmonella enterica Serovar Enteritidis , 2013, PloS one.

[118]  D. Haber,et al.  DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development , 1999, Cell.

[119]  D. Russell,et al.  The detection of extremely rare DNA modifications. Methylation in dam- and hsd- Escherichia coli strains. , 1989, Journal of Biological Chemistry.

[120]  Kazuhiko Sugimoto,et al.  Transcriptional activation mediated by binding of a plant GATA-type zinc finger protein AGP1 to the AG-motif (AGATCCAA) of the wound-inducible Myb gene NtMyb2. , 2003, The Plant journal : for cell and molecular biology.

[121]  Zhenping Chen,et al.  N6‐methyladenine functions as a potential epigenetic mark in eukaryotes , 2015, BioEssays : news and reviews in molecular, cellular and developmental biology.

[122]  P. Hagerman,et al.  Helix rigidity of DNA: the meroduplex as an experimental paradigm. , 1996, Journal of molecular biology.

[123]  R. Shapiro,et al.  The deamination of cytidine and cytosine by acidic buffer solutions. Mutagenic implications. , 1966, Biochemistry.

[124]  O. Elemento,et al.  Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons , 2012, Cell.

[125]  M. Ehrlich,et al.  Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. , 1982, Nucleic acids research.

[126]  D. Patel,et al.  Dual Binding of Chromomethylase Domains to H3K9me2-Containing Nucleosomes Directs DNA Methylation in Plants , 2012, Cell.

[127]  Chengqi Yi,et al.  Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA , 2008, Nature.

[128]  Andrej Sali,et al.  Enzymatic deamination of the epigenetic base N-6-methyladenine. , 2011, Journal of the American Chemical Society.

[129]  S. Diekmann DNA methylation can enhance or induce DNA curvature. , 1987, The EMBO journal.

[130]  N. Lopatina,et al.  On heterogeneity of DNA methylases from Escherichia coli SK cells , 1981, Molecular and Cellular Biochemistry.

[131]  J. Bujnicki,et al.  Novel non-specific DNA adenine methyltransferases , 2011, Nucleic acids research.

[132]  A. Bird DNA methylation patterns and epigenetic memory. , 2002, Genes & development.

[133]  U. Schibler,et al.  A glycosylated liver-specific transcription factor stimulates transcription of the albumin gene , 1989, Cell.

[134]  A. Razin,et al.  Methylated bases in mycoplasmal DNA. , 1980, Nucleic acids research.

[135]  J. P. Jackson,et al.  Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase , 2002, Nature.

[136]  B Nyberg,et al.  Heat-induced deamination of cytosine residues in deoxyribonucleic acid. , 1974, Biochemistry.

[137]  A Janulaitis,et al.  Cytosine modification in DNA by BcnI methylase yields N 4‐methylcytosine , 1983, FEBS letters.

[138]  G. R. Wyatt Occurrence of 5-Methyl-Cytosine in Nucleic Acids , 1950, Nature.

[139]  E. Fleissner,et al.  A new enzyme of RNA synthesis: RNA methylase. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[140]  Chuan He,et al.  Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine , 2011, Science.

[141]  J. Wells,et al.  Molecular analysis of N6-methyladenine patterns in Tetrahymena thermophila nuclear DNA , 1989, Molecular and cellular biology.

[142]  N. Kleckner,et al.  E. coli oriC and the dnaA gene promoter are sequestered from dam methyltransferase following the passage of the chromosomal replication fork , 1990, Cell.

[143]  G. R. Wyatt,et al.  A New Pyrimidine Base from Bacteriophage Nucleic Acids , 1952, Nature.

[144]  P. Modrich,et al.  Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[145]  S. Hattman,et al.  [6N]METHYL ADENINE IN THE NUCLEAR DNA OF A EUCARYOTE, TETRAHYMENA PYRIFORMIS , 1973, The Journal of cell biology.

[146]  Yang Shi,et al.  DNA N6-methyladenine: a new epigenetic mark in eukaryotes? , 2015, Nature Reviews Molecular Cell Biology.

[147]  M. W. van der Woude,et al.  Dam- and OxyR-Dependent Phase Variation of agn43: Essential Elements and Evidence for a New Role of DNA Methylation , 2002, Journal of bacteriology.

[148]  M. Saparbaev,et al.  Excision of hypoxanthine from DNA containing dIMP residues by the Escherichia coli, yeast, rat, and human alkylpurine DNA glycosylases. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[149]  E. Boye,et al.  The role of dam methyltransferase in the control of DNA replication in E. coli , 1990, Cell.

[150]  J. Hurwitz,et al.  The enzymatic methylation of RNA and DNA. , 1963, Biochemical and biophysical research communications.

[151]  A. Jeltsch,et al.  The Escherichia coli dam DNA methyltransferase modifies DNA in a highly processive reaction. , 2002, Journal of molecular biology.

[152]  T. Bestor,et al.  DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. , 1997, Journal of molecular biology.

[153]  Erling Seeberg,et al.  AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli , 2002, Nature.

[154]  B. Vanyushin,et al.  5-Methylcytosine and 6-Methylaminopurine in Bacterial DNA , 1968, Nature.

[155]  A. Benabid,et al.  Bacterial DNA methylation and gene transfer efficiency. , 2000, Biochemical and biophysical research communications.

[156]  C. Bugg,et al.  Conformation of N6-Methyladenine, a Base Involved in DNA Modification: Restriction Processes , 1973, Science.

[157]  T. Matsuda,et al.  Cytokine induction by a bacterial DNA-specific modified base. , 2005, Biochemical and biophysical research communications.

[158]  H. Grosjean Nucleic Acids Are Not Boring Long Polymers of Only Four Types of Nucleotides: A Guided Tour , 2013 .

[159]  Elizabeth C. Theil,et al.  STUDIES ON 6-METHYLAMINOPURINE (6-METHYLADENINE) IN BACTERIAL DEOXYRIBONUCLEIC ACID. , 1963, The Journal of biological chemistry.

[160]  A. Bird,et al.  Use of restriction enzymes to study eukaryotic DNA methylation: I. The methylation pattern in ribosomal DNA from Xenopus laevis. , 1978, Journal of molecular biology.

[161]  Peer Bork,et al.  Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy , 2011, Nucleic Acids Res..

[162]  Robert P. Hausinger,et al.  Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage , 2002, Nature.

[163]  Chuan He,et al.  FTO-Mediated Formation of N6-Hydroxymethyladenosine and N6-Formyladenosine in Mammalian RNA , 2013, Nature Communications.

[164]  D. W. Smith,et al.  Methylation of GATC sites is required for precise timing between rounds of DNA replication in Escherichia coli , 1989, Journal of bacteriology.

[165]  H. Krokan,et al.  AlkB demethylases flip out in different ways. , 2008, DNA repair.

[166]  H. Blom,et al.  Cytosine DNA Methylation Is Found in Drosophila melanogaster but Absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Other Yeast Species , 2014, Analytical chemistry.

[167]  P. V. von Hippel,et al.  Effects of methylation on the stability of nucleic acid conformations. Studies at the polymer level. , 1978, The Journal of biological chemistry.

[168]  V. Ingram,et al.  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. , 1988, Journal of molecular biology.

[169]  J. Hurwitz,et al.  THE ENZYMATIC METHYLATION OF RIBONUCLEIC ACID AND DEOXYRIBONUCLEIC ACID. V. PURIFICATION AND PROPERTIES OF THE DEOXYRIBONUCLEIC ACID-METHYLATING ACTIVITY OF ESCHERICHIA COLI. , 1964, The Journal of biological chemistry.

[170]  T. Orr-Weaver,et al.  Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis , 2011, Proceedings of the National Academy of Sciences.

[171]  R. Burdon,et al.  Methylation of mosquito DNA. , 1979, Biochimica et biophysica acta.

[172]  Frank Lyko,et al.  Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond , 2015, Epigenetics & Chromatin.

[173]  P. Lebreton,et al.  Ultraviolet photoelectron studies of biological purines: the valence electronic structure of adenine. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[174]  M. Graham,et al.  Adenine methylation atdam sites increases transient gene expression in plant cells , 1995, Transgenic Research.

[175]  G. Fazakerley,et al.  The GTm6AC sequence is overwound and bent. , 1989, Nucleic acids research.

[176]  A. Piekarowicz,et al.  The role of Dam methylation in phase variation of Haemophilus influenzae genes involved in defence against phage infection. , 2005, Microbiology.

[177]  H. Grosjean RNA modification: the Golden Period 1995–2015 , 2015, RNA: A publication of the RNA Society.

[178]  S. Hattman,et al.  Sequence specificity of DNA adenine methylase in the protozoan Tetrahymena thermophila , 1982, Journal of bacteriology.

[179]  D. B. Dunn,et al.  Occurrence of a New Base in the Deoxyribonucleic Acid of a Strain of Bacterium Coli , 1955, Nature.

[180]  R. Teoule,et al.  A proton 2D-NMR study of an oligodeoxyribonucleotide containing N6-methyladenine:d(GGm6ATATCC). , 1985, Biochimie.

[181]  L. Aravind,et al.  Natural history of eukaryotic DNA methylation systems. , 2011, Progress in molecular biology and translational science.

[182]  J. Beechem,et al.  Direct Real Time Observation of Base Flipping by theEcoRI DNA Methyltransferase* , 1998, The Journal of Biological Chemistry.

[183]  L. Sowers,et al.  Photochemical deamination and demethylation of 5-methylcytosine. , 1996, Chemical research in toxicology.

[184]  W. Arber,et al.  Host specificity of DNA produced by Escherichia coli. XV. The role of nucleotide methylation in in vitro B-specific modification. , 1972, Journal of molecular biology.

[185]  R. Hotchkiss The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. , 1948, The Journal of biological chemistry.

[186]  Arne Klungland,et al.  ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. , 2013, Molecular cell.

[187]  W. Salser,et al.  The primary sequence of rabbit α-globin mRNA , 1978, Cell.

[188]  M. Meselson,et al.  Effects of high levels of DNA adenine methylation on methyl-directed mismatch repair in Escherichia coli. , 1983, Genetics.

[189]  R. Baur,et al.  Methylated bases in the DNA of the ciliate Stylonychia mytilus. , 1981, European journal of cell biology.

[190]  Miao Yu,et al.  A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation , 2013, Nature chemical biology.

[191]  J. Salinas,et al.  The distribution of 5-methylcytosine in the nuclear genome of plants. , 1992, Nucleic acids research.

[192]  G. Romanov,et al.  Methylation of reiterated sequences in mammalian DNAs. Effects of the tissue type, age, malignancy and hormonal induction. , 1981, Biochimica et biophysica acta.

[193]  P. Bates,et al.  Reversal of DNA alkylation damage by two human dioxygenases , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[194]  M. Radman,et al.  Induced mutagenesis in dam− mutants of Escherichia coli: A role for 6-methyladenine residues in mutation avoidance , 1978, Molecular and General Genetics MGG.

[195]  L. Aravind,et al.  DNA Methylation on N6-Adenine in C. elegans , 2015, Cell.

[196]  Yi Zhang,et al.  Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification , 2010, Nature.

[197]  J. Rabinowitz,et al.  Biosynthesis of ribosylthymine in the transfer RNA of Streptococcus faecalis: a folate-dependent methylation not involving S-adenosylmethionine. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[198]  Yi Zhang,et al.  Mechanisms of epigenetic inheritance. , 2007, Current opinion in cell biology.

[199]  P. Modrich,et al.  Extent of equilibrium perturbation of the DNA helix upon enzymatic methylation of adenine residues. , 1985, The Journal of biological chemistry.

[200]  J. Essigmann,et al.  The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond* , 2015, The Journal of Biological Chemistry.

[201]  J. Bujnicki,et al.  MODOMICS: a database of RNA modification pathways—2013 update , 2012, Nucleic Acids Res..

[202]  S. Linn,et al.  Host specificity of DNA produced by Escherichia coli. XI. In vitro modification of phage fd replicative form. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[203]  M. Marinus Adenine methylation of Okazaki fragments in Escherichia coli , 1976, Journal of bacteriology.

[204]  Yun-Gui Yang,et al.  N6-methyl-adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function , 2012, Genom. Proteom. Bioinform..

[205]  P. Modrich,et al.  Recognition sequence of the dam methylase of Escherichia coli K12 and mode of cleavage of Dpn I endonuclease. , 1979, The Journal of biological chemistry.

[206]  M. Ehrlich,et al.  N4-methylcytosine as a minor base in bacterial DNA , 1987, Journal of bacteriology.

[207]  M. Marinus,et al.  Biological function for 6-methyladenine residues in the DNA of Escherichia coli K12. , 1974, Journal of molecular biology.

[208]  T. Yajima,et al.  Determination of 6-methyladenine in DNA by high-performance liquid chromatography. , 1979, Journal of chromatography.