Skip to main content
SpringerLink
Log in

Evidence for Noncytosine Epigenetic DNA Modifications in Multicellular Eukaryotes: An Overview

  • Protocol
  • First Online:
DNA Modifications

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2198))

Abstract

Cytosine DNA methylation (5-methylcytsone, 5mC) is the major DNA modification found in the genomes of animals and plants. Although the roles of 5mC and its oxidized derivatives in the regulation of gene expression are relatively well attested and extensively explored, a number of recent studies imply that noncytosine DNA modifications may also convey specific biological functions and act as “epigenetic” marks in multicellular organisms. Here we review experimental evidence for the presence of noncytosine epigenetic modifications in metazoans and plants focusing on two “unusual” DNA bases, 5-hydroxymethyluracil (5hmU) and N6-methyladenine (6mA), and suggest potential explanations for inconsistencies in the currently available data on abundance and potential biological roles of these DNA modifications in mammals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gommers-Ampt JH, Borst P (1995) Hypermodified bases in DNA. FASEB J 9:1034–1042. https://doi.org/10.1096/fasebj.9.11.7649402

    Article  CAS  PubMed  Google Scholar 

  2. Fu Y, He C (2012) Nucleic acid modifications with epigenetic significance. Curr Opin Chem Biol 16:516–524. https://doi.org/10.1016/j.cbpa.2012.10.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930. https://doi.org/10.1126/science.1169786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tahiliani M, Koh K, Shen Y et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935. https://doi.org/10.1126/science.1170116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ito S, Shen L, Dai Q et al (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300–1303. https://doi.org/10.1126/science.1210597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. He Y-F, Li B-Z, Li Z et al (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333:1303–1307. https://doi.org/10.1126/science.1210944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Song J, Pfeifer GP (2016) Are there specific readers of oxidized 5-methylcytosine bases? BioEssays 38:1038–1047. https://doi.org/10.1002/bies.201600126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Klungland A, Robertson AB (2017) Oxidized C5-methyl cytosine bases in DNA: 5-hydroxymethylcytosine; 5-formylcytosine; and 5-carboxycytosine. Free Radic Biol Med 107:62–68. https://doi.org/10.1016/j.freeradbiomed.2016.11.038

    Article  CAS  PubMed  Google Scholar 

  9. Pfaffeneder T, Spada F, Wagner M et al (2014) Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA. Nat Chem Biol 10:574–581. https://doi.org/10.1038/nchembio.1532

    Article  CAS  PubMed  Google Scholar 

  10. Mullaart E, Lohman PH, Berends F, Vijg J (1990) DNA damage metabolism and aging. Mutat Res 237:189–210. https://doi.org/10.1016/0921-8734(90)90001-8

    Article  CAS  PubMed  Google Scholar 

  11. Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging (cancer/mutation/endogenous DNA adducts/oxygen radicals). Proc Natl Acad Sci U S A 90:7915–7922

    Article  CAS  Google Scholar 

  12. Cadet J, Wagner JR (2014) Oxidatively generated base damage to cellular DNA by hydroxyl radical and one-electron oxidants: similarities and differences. Arch Biochem Biophys 557:47–54. https://doi.org/10.1016/j.abb.2014.05.001

    Article  CAS  PubMed  Google Scholar 

  13. Olinski R, Starczak M, Gackowski D (2016) Enigmatic 5-hydroxymethyluracil: oxidatively modified base, epigenetic mark or both? Mutat Res Rev Mutat Res 767:59–66. https://doi.org/10.1016/j.mrrev.2016.02.001

    Article  CAS  PubMed  Google Scholar 

  14. Cliffe LJ, Hirsch G, Wang J et al (2012) JBP1 and JBP2 proteins are Fe 2+ /2-oxoglutarate-dependent dioxygenases regulating hydroxylation of thymidine residues in trypanosome DNA. J Biol Chem 287:19886–19895. https://doi.org/10.1074/jbc.M112.341974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ulbert S, Eide L, Seeberg E, Borst P (2004) Base J, found in nuclear DNA of Trypanosoma brucei, is not a target for DNA glycosylases. DNA Repair (Amst) 3:145–154. https://doi.org/10.1016/j.dnarep.2003.10.009

    Article  CAS  Google Scholar 

  16. van Leeuwen F, Kieft R, Cross M, Borst P (1998) Biosynthesis and function of the modified DNA base β-d-glucosyl-hydroxymethyluracil in Trypanosoma brucei. Mol Cell Biol 18:5643–5651. https://doi.org/10.1128/mcb.18.10.5643

    Article  PubMed  PubMed Central  Google Scholar 

  17. Borst P, Sabatini R (2008) Base J: discovery, biosynthesis, and possible functions. Annu Rev Microbiol 62:235–251. https://doi.org/10.1146/annurev.micro.62.081307.162750

    Article  CAS  PubMed  Google Scholar 

  18. Van Luenen HGAM, Farris C, Jan S et al (2012) Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania. Cell 150:909–921. https://doi.org/10.1016/j.cell.2012.07.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kawasaki F, Beraldi D, Hardisty RE et al (2017) Genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite Leishmania. Genome Biol 18:1–8. https://doi.org/10.1186/s13059-017-1150-1

    Article  CAS  Google Scholar 

  20. Guo JU, Su Y, Zhong C et al (2011) Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145:423–434. https://doi.org/10.1016/j.cell.2011.03.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cortellino S, Xu J, Sannai M et al (2011) Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 146:67–79

    Article  CAS  Google Scholar 

  22. Hollstein MC, Brooks P, Linn S, Ames BN (1984) Hydroxymethyluracil DNA glycosylase in mammalian cells. Proc Natl Acad Sci U S A 81:4003–4007. https://doi.org/10.1073/pnas.81.13.4003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Boorstein RJ, Levy DD, Teebor GW (1987) 5-Hydroxymethyluracil-DNA glycosylase activity may be a differentiated mammalian function. Mutat Res 183:257–263. https://doi.org/10.1016/0167-8817(87)90008-3

    Article  CAS  PubMed  Google Scholar 

  24. Rusmintratip V, Sowers LC (2000) An unexpectedly high excision capacity for mispaired 5-hydroxymethyluracil in human cell extracts. Proc Natl Acad Sci U S A 97:14183–14187. https://doi.org/10.1073/pnas.97.26.14183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kemmerich K, Dingler FA, Rada C, Neuberger MS (2012) Germline ablation of SMUG1 DNA glycosylase causes loss of 5-hydroxymethyluracil-and UNG-backup uracil-excision activities and increases cancer predisposition of Ung−/−Msh2−/− mice. Nucleic Acids Res 40:6016–6025. https://doi.org/10.1093/nar/gks259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Doseth B, Visnes T, Wallenius A et al (2011) Uracil-DNA glycosylase in base excision repair and adaptive immunity: species differences between man and mouse. J Biol Chem 286:16669–16680. https://doi.org/10.1074/jbc.M111.230052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Alsøe L, Sarno A, Carracedo S et al (2017) Uracil accumulation and mutagenesis dominated by cytosine deamination in CpG Dinucleotides in mice lacking UNG and SMUG1. Sci Rep 7:7199. https://doi.org/10.1038/s41598-017-07314-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nabel CS, Manning SA, Kohli RM (2012) The curious chemical biology of cytosine: deamination, methylation, and oxidation as modulators of genomic potential. ACS Chem Biol 7:20–30. https://doi.org/10.1021/cb2002895

    Article  CAS  PubMed  Google Scholar 

  29. Franchini DM, Petersen-Mahrt SK (2014) AID and APOBEC deaminases: balancing DNA damage in epigenetics and immunity. Epigenomics 6:427–443. https://doi.org/10.2217/epi.14.35

    Article  CAS  PubMed  Google Scholar 

  30. Grin I, Ishchenko AA (2016) An interplay of the base excision repair and mismatch repair pathways in active DNA demethylation. Nucleic Acids Res 44:3713–3727. https://doi.org/10.1093/nar/gkw059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Boorstein RJ, Chiu LN, Teebor GW (1989) Phylogenetic evidence of a role for 5-hydroxymethyluracil-DNA glycosylase in the maintenance of 5-methylcytosine in DNA. Nucleic Acids Res 17:7653–7661

    Article  CAS  Google Scholar 

  32. Birnbaum GI, Deslauriers R, Lin TS et al (1980) A novel intramolecular hydrogen bond in the crystal structure of 5-hydroxymethyl-2′-deoxyuridine, an antiviral and antineoplastic nucleoside. Conformational analysis of the deoxyribose ring. J Am Chem Soc 102:4236–4241. https://doi.org/10.1021/ja00532a041

    Article  CAS  Google Scholar 

  33. Klose RJ, Sarraf SA, Schmiedeberg L et al (2005) DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG. Mol Cell 19:667–678

    Article  CAS  Google Scholar 

  34. Greer EL, Blanco MA, Gu L et al (2015) DNA methylation on N6-adenine in C. elegans. Cell 161:868–878. https://doi.org/10.1016/j.cell.2015.04.005

    Article  CAS  Google Scholar 

  35. Zhang G, Huang H, Liu D et al (2015) N6-methyladenine DNA modification in Drosophila. Cell 161:893–906. https://doi.org/10.1016/j.cell.2015.04.018

    Article  CAS  PubMed  Google Scholar 

  36. Yao B, Li Y, Wang Z et al (2018) Active N 6 -methyladenine demethylation by DMAD regulates gene expression by coordinating with Polycomb protein in neurons. Mol Cell 71:848–857.e6. https://doi.org/10.1016/j.molcel.2018.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shah K, Cao W, Ellison CE (2019) Adenine methylation in drosophila is associated with the tissue-specific expression of developmental and regulatory genes. G3 (Bethesda) 9:1893–1900. https://doi.org/10.1534/g3.119.400023

    Article  CAS  PubMed Central  Google Scholar 

  38. Liu J, Zhu Y, Luo GZ et al (2016) Abundant DNA 6mA methylation during early embryogenesis of zebrafish and pig. Nat Commun 7:1–7. https://doi.org/10.1038/ncomms13052

    Article  CAS  Google Scholar 

  39. Wu TP, Wang T, Seetin MG et al (2016) DNA methylation on N6-adenine in mammalian embryonic stem cells. Nature 532:329–333. https://doi.org/10.1038/nature17640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Xiao C-L, Zhu S, He M et al (2018) N(6)-methyladenine DNA modification in the human genome. Mol Cell 71:306–318. https://doi.org/10.1016/j.molcel.2018.06.015

    Article  CAS  PubMed  Google Scholar 

  41. Xie Q, Wu TP, Gimple RC et al (2018) N6-methyladenine DNA modification in glioblastoma. Cell 175:1228–1243.e20. https://doi.org/10.1016/j.cell.2018.10.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Koziol MJ, Bradshaw CR, Allen GE et al (2016) Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 23:24–30. https://doi.org/10.1038/nsmb.3145

    Article  CAS  PubMed  Google Scholar 

  43. O’Brown ZK, Greer EL (2016) N6-Methyladenine: a conserved and dynamic DNA mark. Adv Exp Med Biol 945:213–246. https://doi.org/10.1007/978-3-319-43624-1_10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Vanyushin BF, Belozersky AN, Kokurina NA, Kadirova DX (1968) 5-Methylcytosine and 6-methylaminopurine in bacterial DNA. Nature 218:1066–1067. https://doi.org/10.1038/2181066a0

    Article  CAS  PubMed  Google Scholar 

  45. Dunn DB, Smith JD (1958) The occurrence of 6-methylaminopurine in deoxyribonucleic acids. Biochem J 68:627–636. https://doi.org/10.1042/bj0680627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Marinus MG, Morris NR (1973) Isolation of deoxyribonucleic acid methylase mutants of Escherichia coli K-12. J Bacteriol 114:1143–1150

    Article  CAS  Google Scholar 

  47. Russell DW, Hirata RK (1989) The detection of extremely rare DNA modifications. Methylation in dam- and hsd- Escherichia coli strains. J Biol Chem 264:10787–10794

    CAS  PubMed  Google Scholar 

  48. Campbell JL, Kleckner N (1990) E. coli oriC and the dnaA gene promoter are sequestered from dam methyltransferase following the passage of the chromosomal replication fork. Cell 62:967–979. https://doi.org/10.1016/0092-8674(90)90271-F

    Article  CAS  PubMed  Google Scholar 

  49. Yamaki H, Ohtsubo E, Nagai K, Maeda Y (1988) The oriC unwinding by dam methylation in Escherichia coli. Nucleic Acids Res 16:5067–5073. https://doi.org/10.1093/nar/16.11.5067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wallecha A, Munster V, Correnti J et al (2002) Dam- and OxyR-dependent phase variation of agn43: essential elements and evidence for a new role of DNA methylation. J Bacteriol 184:3338–3347. https://doi.org/10.1128/JB.184.12.3338-3347.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Robbins-Manke JL, Zdraveski ZZ, Marinus M, Essigmann JM (2005) Analysis of global gene expression and double-strand-break formation in DNA adenine methyltransferase- and mismatch repair-deficient Escherichia coli. J Bacteriol 187:7027–7037. https://doi.org/10.1128/JB.187.20.7027-7037.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Roberts D (1985) IS10 transposition IS regulated by DNA adenine methylation. Cell 43:117–130. https://doi.org/10.1016/0092-8674(85)90017-0

    Article  CAS  PubMed  Google Scholar 

  53. Pukkila PJ, Peterson J, Herman G et al (1983) Effects of high levels of DNA adenine methylation on methyl-directed mismatch repair in Escherichia coli. Genetics 104:571–582

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Messer W, Noyer-Weidner M (1988) Timing and targeting: the biological functions of Dam methylation in E. coli. Cell 54:735–737. https://doi.org/10.1016/S0092-8674(88)90911-7

    Article  CAS  PubMed  Google Scholar 

  55. Sarnacki SH, Castañeda M del RA, Llana MN et al (2013) Dam methylation participates in the regulation of PmrA/PmrB and RcsC/RcsD/RcsB two component regulatory systems in Salmonella enterica Serovar Enteritidis. PLoS One 8:e56474. https://doi.org/10.1371/journal.pone.0056474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Luria SE, Human ML (1952) A nonhereditary, host-induced variation of bacterial viruses. J Bacteriol 64:557–569

    Article  CAS  Google Scholar 

  57. Meselson M, Yuan R (1968) DNA restriction enzyme from E. coli. Nature 217:1110–1114. https://doi.org/10.1038/2171110a0

    Article  CAS  Google Scholar 

  58. Linn S, Arber W (1968) Host specificity of DNA produced by Escherichia coli, X. In vitro restriction of phage fd replicative form. Proc Natl Acad Sci 59:1300–1306. https://doi.org/10.1073/pnas.59.4.1300

    Article  CAS  PubMed  Google Scholar 

  59. Smith JD, Arber W, Kühnlein U (1972) Host specificity of DNA produced by Escherichia coli. J Mol Biol 63:1–8. https://doi.org/10.1016/0022-2836(72)90517-7

    Article  CAS  PubMed  Google Scholar 

  60. Zaleski P, Wojciechowski M, Piekarowicz A (2005) The role of Dam methylation in phase variation of Haemophilus influenzae genes involved in defence against phage infection. Microbiology 151:3361–3369. https://doi.org/10.1099/mic.0.28184-0

    Article  CAS  PubMed  Google Scholar 

  61. Rae PMM, Spear BB (1978) Macronuclear DNA of the hypotrichous ciliate Oxytricha fallax. Proc Natl Acad Sci 75:4992–4996. https://doi.org/10.1073/pnas.75.10.4992

    Article  CAS  PubMed  Google Scholar 

  62. Gorovsky MA, Hattman S, Pleger GL (1973) (6 N)methyl adenine in the nuclear DNA of a eucaryote, Tetrahymena pyriformis. J Cell Biol 56:697–701. https://doi.org/10.1083/jcb.56.3.697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ammermann D, Steinbrück G, Baur R, Wohlert H (1981) Methylated bases in the DNA of the ciliate Stylonychia mytilus. Eur J Cell Biol 24:154–156

    CAS  PubMed  Google Scholar 

  64. Fu Y, Luo G-Z, Chen K et al (2015) N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas. Cell 161:879–892. https://doi.org/10.1016/j.cell.2015.04.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhou C, Wang C, Liu H et al (2018) Identification and analysis of adenine N 6-methylation sites in the rice genome. Nat Plants 4:554–563. https://doi.org/10.1038/s41477-018-0214-x

    Article  CAS  PubMed  Google Scholar 

  66. Seidl MF (2017) Adenine N6-methylation in diverse fungi. Nat Genet 49:823–824. https://doi.org/10.1038/ng.3873

    Article  CAS  PubMed  Google Scholar 

  67. Mondo SJ, Dannebaum RO, Kuo RC et al (2017) Widespread adenine N6-methylation of active genes in fungi. Nat Genet 49:964–968. https://doi.org/10.1038/ng.3859

    Article  CAS  PubMed  Google Scholar 

  68. Cummings DJ, Tait A, Goddard JM (1974) Methylated bases in DNA from Paramecium aurelia. Biochim Biophys Acta 374:1–11. https://doi.org/10.1016/0005-2787(74)90194-4

    Article  CAS  PubMed  Google Scholar 

  69. Van Etten JL, Schuster AM, Girton L et al (1985) DNA methylation of viruses infecting a eukaryotic chlorella -like green alga. Nucleic Acids Res 13:3471–3478. https://doi.org/10.1093/nar/13.10.3471

    Article  PubMed  PubMed Central  Google Scholar 

  70. Liang Z, Shen L, Cui X et al (2018) DNA N6-adenine methylation in Arabidopsis thaliana. Dev Cell 45:406–416.e3. https://doi.org/10.1016/j.devcel.2018.03.012

    Article  CAS  PubMed  Google Scholar 

  71. Zilberman D, Gehring M, Tran RK et al (2007) Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription. Nat Genet 39:61–69. https://doi.org/10.1038/ng1929

    Article  CAS  PubMed  Google Scholar 

  72. Yao B, Cheng Y, Wang Z et al (2017) DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress. Nat Commun 8:1–10. https://doi.org/10.1038/s41467-017-01195-y

    Article  CAS  Google Scholar 

  73. Kweon SM, Chen Y, Moon E et al (2019) An adversarial DNA N6-Methyladenine-sensor network preserves polycomb silencing. Mol Cell 74:1138–1147.e6. https://doi.org/10.1016/j.molcel.2019.03.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ratel D, Ravanat J-L, Berger F, Wion D (2006) N6-methyladenine: the other methylated base of DNA. BioEssays 28:309–315. https://doi.org/10.1002/bies.20342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Schiffers S, Ebert C, Rahimoff R et al (2017) Quantitative LC-MS provides no evidence for m 6 dA or m 4 dC in the genome of mouse embryonic stem cells and tissues. Angew Chemie Int Ed Engl 56:11268–11271. https://doi.org/10.1002/anie.201700424

    Article  CAS  Google Scholar 

  76. Lentini A, Lagerwall C, Vikingsson S et al (2018) A reassessment of DNA-immunoprecipitation-based genomic profiling. Nat Methods 15:499–504. https://doi.org/10.1038/s41592-018-0038-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. O’Brown ZK, Boulias K, Wang J et al (2019) Sources of artifact in measurements of 6mA and 4mC abundance in eukaryotic genomic DNA. BMC Genomics 20:445. https://doi.org/10.1186/s12864-019-5754-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Charles MP, Ravanat JL, Adamski D et al (2004) N(6)-Methyldeoxyadenosine, a nucleoside commonly found in prokaryotes, induces C2C12 myogenic differentiation. Biochem Biophys Res Commun 314:476–482. https://doi.org/10.1016/j.bbrc.2003.12.132

    Article  CAS  PubMed  Google Scholar 

  79. Abakir A, Giles TC, Cristini A et al (2020) N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nat Genet 52:48–55. https://doi.org/10.1038/s41588-019-0549-x

    Article  CAS  PubMed  Google Scholar 

  80. Liu J, Dou X, Chen C et al (2020) N (6)-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367(6477):580–586. https://doi.org/10.1126/science.aay6018

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

A.R.’s lab is supported by Biotechnology and Biological Sciences Research Council [grant number BB/N005759/1] to A.R.

Author information

Authors and Affiliations

  1. Division of Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, University Park, UK

    Paige Lowe & Alexey Ruzov

  2. Department of Clinical Biochemistry, Faculty of Pharmacy, Nicolaus Copernicus University in Torun, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland

    Ryszard Olinski

Authors
  1. Paige Lowe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryszard Olinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexey Ruzov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ryszard Olinski or Alexey Ruzov .

Editor information

Editors and Affiliations

  1. Centre for Biomolecular Sciences, University Park, University of Nottingham, Nottingham, UK

    Alexey Ruzov

  2. School of Life Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, UK

    Martin Gering

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Lowe, P., Olinski, R., Ruzov, A. (2021). Evidence for Noncytosine Epigenetic DNA Modifications in Multicellular Eukaryotes: An Overview. In: Ruzov, A., Gering, M. (eds) DNA Modifications. Methods in Molecular Biology, vol 2198. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0876-0_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0876-0_2

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0875-3

  • Online ISBN: 978-1-0716-0876-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation