The exploration of N6-deoxyadenosine methylation in mammalian genomes
Xuwen Li, Zijian Zhang, Xinlong Luo, Jacob Schrier, Andrew D. Yang, Tao P. Wu
The exploration of N6-deoxyadenosine methylation in mammalian genomes
N6-methyladenine (N6-mA, m6dA, or 6mA), a prevalent DNA modification in prokaryotes, has recently been identified in higher eukaryotes, including mammals. Although 6mA has been well-studied in prokaryotes, the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood. Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes, from transposable-element suppression to environmental stress response. Here, we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes, predominantly mammals.
DNA N6-methyladenine (6mA) / mammalian DNA modification / non-canonical mammalian DNA methylation
[1] |
Abakir A, Giles TC, Cristini A, Foster JM, Dai N, Starczak M, Rubio-Roldan A, Li M, Eleftheriou M, Crutchley J
CrossRef
Google scholar
|
[2] |
Beh LY, Debelouchina GT, Clay DM, Thompson RE, Lindblad KA, Hutton ER, Bracht JR, Sebra RP, Muir TW, Landweber LF(2019) Identification of a DNA N6-adenine methyltransferase complex and its impact on chromatin organization. Cell 177:1781–1796
CrossRef
Google scholar
|
[3] |
Boyer HW(1971) DNA restriction and modification mechanisms in bacteria. Annu Rev Microbiol 25:153–176
CrossRef
Google scholar
|
[4] |
Bromberg S, Pratt K, Hattman S(1982) Sequence specificity of DNA adenine methylase in the protozoan Tetrahymena thermophila. J Bacteriol 150:993–996
CrossRef
Google scholar
|
[5] |
Charles MP, Ravanat JL, Adamski D, D’Orazi G, Cadet J, Favier A, Berger F, Wion D(2004) N6-methyldeoxyadenosine, a nucleoside commonly found in prokaryotes, induces C2C12 myogenic differentiation. Biochem Biophys Res Commun 314:476–482
CrossRef
Google scholar
|
[6] |
Chen L, Zhang M, Guo M(2020) DNA N6-methyladenine epigenetic modification elevated in human esophageal squamous cell carcinoma: a potential prognostic marker. Discov Med 157:85–90
|
[7] |
Diekmann S(1987) DNA methylation can enhance or induce DNA curvature. EMBO J 6:4213–4217
CrossRef
Google scholar
|
[8] |
Douvlataniotis K, Bensberg M, Lentini A, Gylemo B, Nestor CE(2020) No evidence for DNA N6-methyladenine in mammals. Sci Adv 6:eaay3335
CrossRef
Google scholar
|
[9] |
Dunn DB, Smith JD(1955) Occurrence of a new base in the deoxyribonucleic acid of a strain of Bacterium coli. Nature 175:336–337
CrossRef
Google scholar
|
[10] |
Dunn DB, Smith JD(1958) The occurrence of 6-methylaminopurine in deoxyribonucleic acids. Biochem J 68:627–636
CrossRef
Google scholar
|
[11] |
Falnes P, Johansen RF, Seeberg E(2002) AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 419:178–182
CrossRef
Google scholar
|
[12] |
Fernandes SB, Grova N, Roth S, Duca RC, Godderis L, Guebels P, Mériaux SB, Lumley AI, Bouillaud-Kremarik P, Ernens I
CrossRef
Google scholar
|
[13] |
Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC, Clark TA, Korlach J, Turner SW(2010) Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods 7:461–465
CrossRef
Google scholar
|
[14] |
Fu Y, Luo GZ, Chen K, Deng X, Yu M, Han D, Hao Z, Liu J, Lu X, Doré LC
CrossRef
Google scholar
|
[15] |
Gorovsky MA, Hattman S, Pleger GL(1973) [6N]methyl adenine in the nuclear DNA of a eucaryote, Tetrahymena Pyriformis. J Cell Biol 56:697–701
CrossRef
Google scholar
|
[16] |
Gray MW(2012) Mitochondrial evolution. Cold Spring Harb Perspect Biol 4:a011403
CrossRef
Google scholar
|
[17] |
Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizábal-Corrales D, Hsu CH, Aravind L, He C, Shi Y(2015) DNA methylation on N6-adenine in C. elegans. Cell 161:868–878
CrossRef
Google scholar
|
[18] |
Hao Z, Wu T, Cui X, Zhu P, Tan C, Dou X, Hsu KW, Te LY, Peng PH, Zhang LS
CrossRef
Google scholar
|
[19] |
He S, Zhang G, Wang J, Gao Y, Sun R, Cao Z, Chen Z, Zheng X, Yuan J, Luo Y
CrossRef
Google scholar
|
[20] |
Hong T, Yuan Y, Wang T, Ma J, Yao Q, Hua X, Xia Y, Zhou X(2016) Selective detection of N6-methyladenine in DNA via metal ionmediated replication and rolling circle amplification. Chem Sci 8:200–205
CrossRef
Google scholar
|
[21] |
Huang W, Xiong J, Yang Y, Liu SM, Yuan BF, Feng YQ(2015) Determination of DNA adenine methylation in genomes of mammals and plants by liquid chromatography/mass spectrometry. RSC Adv 5:64046–64054
CrossRef
Google scholar
|
[22] |
Im K, Mareninov S, Diaz MFP, Yong WH(2019) An introduction to performing immunofluorescence staining. Methods Mol Biol 1897:299–311
CrossRef
Google scholar
|
[23] |
Koh CWQ, Goh YT, Toh JDW, Neo SP, Ng SB, Gunaratne J, Gao YG, Quake SR, Burkholder WF, Goh WSS(2018) Singlenucleotide-resolution sequencing of human N6-methyldeoxyadenosine reveals strand-asymmetric clusters associated with SSBP1 on the mitochondrial genome. Nucleic Acids Res 46:11659–11670
CrossRef
Google scholar
|
[24] |
Koziol MJ, Bradshaw CR, Allen GE, Costa ASH, Frezza C, Gurdon JB(2016) Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 23:24–30
CrossRef
Google scholar
|
[25] |
Kramer B, Kramer W, Fritz HJ(1984) Different base/base mismatches are corrected with different efficiencies by the methyldirected DNA mismatch-repair system of E. coli. Cell 38:879–887
CrossRef
Google scholar
|
[26] |
Kulis M, Esteller M(2010) DNA methylation and cancer. Adv Genet 70:27–56
CrossRef
Google scholar
|
[27] |
Kweon SM, Chen Y, Moon E, Kvederaviciutė K, Klimasauskas S, Feldman DE(2019) An adversarial DNA N6-methyladeninesensor network preserves polycomb silencing. Mol Cell 74:1138–1147
CrossRef
Google scholar
|
[28] |
Li E, Zhang Y(2014) DNA methylation in mammals. Cold Spring Harb Perspect Biol 6:a019133
CrossRef
Google scholar
|
[29] |
Li W, Shi Y, Zhang T, Ye J, Ding J(2019a) Structural insight into human N6amt1–Trm112 complex functioning as a protein methyltransferase. Cell Discov 5:1–13
CrossRef
Google scholar
|
[30] |
Li X, Zhao Q, Wei W, Lin Q, Magnan C, Emami MR, Wearick-Silva LE, Viola TW, Marshall PR, Yin J
CrossRef
Google scholar
|
[31] |
Li H, Wu Z, Liu X, Zhang S, Ji Q, Jiang X, Liu Z, Wang S, Qu J, Zhang W
CrossRef
Google scholar
|
[32] |
Li Z, Zhao S, Nelakanti RV, Lin K, Wu TP, Alderman MH, Guo C, Wang P, Zhang M, Min W
CrossRef
Google scholar
|
[33] |
Liang D, Wang H, Song W, Xiong X, Zhang X, Hu Z, Guo H, Yang Z, Zhai S, Zhang LH
CrossRef
Google scholar
|
[34] |
Liang Z, Shen L, Cui X, Bao S, Geng Y, Yu G, Liang F, Xie S, Lu T, Gu X
CrossRef
Google scholar
|
[35] |
Liu J, Zhu Y, Luo GZ, Wang X, Yue Y, Wang X, Zong X, Chen K, Yin H, Fu Y
CrossRef
Google scholar
|
[36] |
Liu B, Liu X, Lai W, Wang H(2017) Metabolically generated stable isotope-labeled deoxynucleoside code for tracing DNA N6-methyladenine in human cells. Anal Chem 89:6202–6209
CrossRef
Google scholar
|
[37] |
Liu Q, Fang L, Yu G, Wang D, Le XC, Wang K(2019) Detection of DNA base modifications by deep recurrent neural network on Oxford Nanopore sequencing data. Nat Commun 10:2449
CrossRef
Google scholar
|
[38] |
Liu X, Lai W, Li Y, Chen S, Liu B, Zhang N, Mo J, Lyu C, Zheng J, Du YR
CrossRef
Google scholar
|
[39] |
Lu M, Campbell JL, Boye E, Kleckner N(1994) SeqA: a negative modulator of replication initiation in E. coli. Cell 77:413–426
CrossRef
Google scholar
|
[40] |
Luo GZ, Wang F, Weng X, Chen K, Hao Z, Yu M, Deng X, Liu J, He C(2016) Characterization of eukaryotic DNA N6-methyladenine by a highly sensitive restriction enzyme-assisted sequencing. Nat Commun 7:11301
CrossRef
Google scholar
|
[41] |
Luo C, Hajkova P, Ecker JR(2018a) Dynamic DNA methylation: in the right place at the right time. Science 361:1336–1340
CrossRef
Google scholar
|
[42] |
Luo GZ, Hao Z, Luo L, Shen M, Sparvoli D, Zheng Y, Zhang Z, Weng X, Chen K, Cui Q
|
[43] |
Ma C, Niu R, Huang T, Shao LW, Peng Y, Ding W, Wang Y, Jia G, He C, Li CY
CrossRef
Google scholar
|
[44] |
Mahdavi-Amiri Y, Chung Kim Chung K, Hili R(2021) Singlenucleotide resolution of: N6-adenine methylation sites in DNA and RNA by nitrite sequencing. Chem Sci 12:606–612
CrossRef
Google scholar
|
[45] |
Marinus MG, Morris NR(1973) Isolation of deoxyribonucleic acid methylase mutants of Escherichia coli K-12. J Bacteriol 114:1143–1150
CrossRef
Google scholar
|
[46] |
Marinus MG, Morris NR(1974) Biological function for 6-methyladenine residues in the DNA of Escherichia coli K12. J Mol Biol 85:309–322
CrossRef
Google scholar
|
[47] |
McIntyre ABR, Alexander N, Grigorev K, Bezdan D, Sichtig H, Chiu CY, Mason CE(2019) Single-molecule sequencing detection of N6-methyladenine in microbial reference materials. Nat Commun 10:579
CrossRef
Google scholar
|
[48] |
Moore LD, Le T, Fan G(2013) DNA methylation and its basic function. Neuropsychopharmacology 38:23–38
CrossRef
Google scholar
|
[49] |
Musheev MU, Baumgärtner A, Krebs L, Niehrs C(2020) The origin of genomic N 6-methyl-deoxyadenosine in mammalian cells. Nat Chem Biol 16:630–634
CrossRef
Google scholar
|
[50] |
Nappi M, Hofer A, Balasubramanian S, Gaunt MJ(2020) Selective chemical functionalization at N6-methyladenosine residues in dna enabled by visible-light-mediated photoredox catalysis. J Am Chem Soc 142:21484–21492
CrossRef
Google scholar
|
[51] |
Ni P, Huang N, Zhang Z, Wang DP, Liang F, Miao Y, Le XC, Luo F, Wang J(2019) DeepSignal: detecting DNA methylation state from Nanopore sequencing reads using deep-learning. Bioinformatics 35:4586–4595
CrossRef
Google scholar
|
[52] |
O’Brown ZK, Boulias K, Wang J, Wang SY, O’Brown NM, Hao Z, Shibuya H, Fady PE, Shi Y, He C
CrossRef
Google scholar
|
[53] |
Rand AC, Jain M, Eizenga JM, Musselman-Brown A, Olsen HE, Akeson M, Paten B(2017) Mapping DNA methylation with highthroughput nanopore sequencing. Nat Methods 14:411–413
CrossRef
Google scholar
|
[54] |
Ratel D, Ravanat JL, Charles MP, Platet N, Breuillaud L, Lunardi J, Berger F, Wion D(2006) Undetectable levels of N6-methyl adenine in mouse DNA: cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase. FEBS Lett 580:3179–3184
CrossRef
Google scholar
|
[55] |
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
CrossRef
Google scholar
|
[56] |
Sánchez-Romero MA, Cota I, Casadesús J(2015) DNA methylation in bacteria: from the methyl group to the methylome. Curr Opin Microbiol 25:9–16
CrossRef
Google scholar
|
[57] |
Schiffers S, Ebert C, Rahimoff R, Kosmatchev O, Steinbacher J, Bohne AV, Spada F, Michalakis S, Nickelsen J, Müller M
CrossRef
Google scholar
|
[58] |
Schübeler D(2015) Function and information content of DNA methylation. Nature 517:321–326
CrossRef
Google scholar
|
[59] |
Sheng X, Wang J, Guo Y, Zhang J, Luo J(2021) DNA N6-methyladenine (6mA) modification regulates drug resistance in triple negative breast cancer. Front Oncol 10:616098
CrossRef
Google scholar
|
[60] |
Smith ZD, Meissner A(2013) DNA methylation: roles in mammalian development. Nat Rev Genet 14:204–220
CrossRef
Google scholar
|
[61] |
Smith JD, Arber W, Kühnlein U(1972) Host specificity of DNA produced by Escherichia coli. XIV. the role of nucleotide methylation in in vivo B-specific modification. J Mol Biol 63:1–8
CrossRef
Google scholar
|
[62] |
Sternberg N(1985) Evidence that adenine methylation influences DNA-protein interactions in Escherichia coli. J Bacteriol 164:490–493
CrossRef
Google scholar
|
[63] |
Stoiber M, Quick J, Egan R, Eun Lee J, Celniker S, Neely R, Loman N, Pennacchio L, Brown J(2016) De novo identification of DNA modifications enabled by genome-guided nanopore signal processing. bioRxiv. https://doi.org/10.1101/094672
CrossRef
Google scholar
|
[64] |
Stott DI(1989) Immunoblotting and dot blotting. J Immunol Methods 119:153–187
CrossRef
Google scholar
|
[65] |
Tian L-F, Liu Y-P, Chen L, Tang Q, Wu W, Sun W, Chen Z, Yan X-X(2020) Structural basis of nucleic acid recognition and 6mA demethylation by human ALKBH1. Cell Res 30:272–275
CrossRef
Google scholar
|
[66] |
Vanyushin BF, Belozersky AN, Kokurina NA, Kadirova DX(1968) 5-methylcytosine and 6-methylaminopurine in bacterial DNA. Nature 218:1066–1067
CrossRef
Google scholar
|
[67] |
Wetzel C, Limbach PA(2016) Mass spectrometry of modified RNAs: recent developments. Analyst 141:16–23
CrossRef
Google scholar
|
[68] |
Woodcock CB, Yu D, Hajian T, Li J, Huang Y, Dai N, Corrêa IR, Wu T, Vedadi M, Zhang X
CrossRef
Google scholar
|
[69] |
Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, Liu Y, Byrum SD, Mackintosh SG, Zhong M
CrossRef
Google scholar
|
[70] |
Xiao CL, Zhu S, He M, Chen D, Zhang Q, Chen Y, Yu G, Liu J, Xie SQ, Luo F
CrossRef
Google scholar
|
[71] |
Xie Q, Wu TP, Gimple RC, Li Z, Prager BC, Wu Q, Yu Y, Wang P, Wang Y, Gorkin DU
CrossRef
Google scholar
|
[72] |
Yao B, Cheng Y, Wang Z, Li Y, Chen L, Huang L, Zhang W, Chen D, Wu H, Tang B
CrossRef
Google scholar
|
[73] |
Yao B, Li Y, Wang Z, Chen L, Poidevin M, Zhang C, Lin L, Wang F, Bao H, Jiao B
CrossRef
Google scholar
|
[74] |
Zhang G, Huang H, Liu D, Cheng Y, Liu X, Zhang W, Yin R, Zhang D, Zhang P, Liu J
CrossRef
Google scholar
|
[75] |
Zhang M, Yang S, Nelakanti R, Zhao W, Liu G, Li Z, Liu X, Wu T, Xiao A, Li H(2020a) Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA. Cell Res 30:197–210
CrossRef
Google scholar
|
[76] |
Zhang Z, Hou Y, Wang Y, Gao T, Ma Z, Yang Y, Zhang P, Yi F, Zhan J, Zhang H
CrossRef
Google scholar
|
[77] |
Zhang X, Blumenthal RM, Cheng X(2021) A role for N6-methyladenine in DNA damage repair. Trends Biochem Sci 46:175–183
CrossRef
Google scholar
|
[78] |
Zhou C, Wang C, Liu H, Zhou Q, Liu Q, Guo Y, Peng T, Song J, Zhang J, Chen L
CrossRef
Google scholar
|
[79] |
Zhu S, Beaulaurier J, Deikus G, Wu TP, Strahl M, Hao Z, Luo G, Gregory JA, Chess A, He C
CrossRef
Google scholar
|
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