Abstract
Nucleotide variants, especially those related to epigenetic functions, provide critical regulatory information beyond simple genomic sequence, and they define cell status in higher organisms. 5-methylcytosine, which is found in DNA, was until recently the only nucleotide variant studied in terms of epigenetics in eukaryotes. However, 5-methylcytosine has turned out to be just one component of a dynamic DNA epigenetic regulatory network that also includes 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Recently, reversible methylation of N6-methyladenosine in RNA has also been demonstrated. The discovery of these new nucleotide variants triggered an explosion of new information in the epigenetics field. This rapid research progress has benefited significantly from timely developments of new technologies that specifically recognize, enrich and sequence nucleotide modifications, as evidenced by the wide application of the bisulfite sequencing of 5-methylcytosine and very recent modifications of bisulfite sequencing to resolve 5-hydroxymethylcytosine from 5-methylcytosine with base-resolution information.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Klose, R.J. & Bird, A.P. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31, 89–97 (2006).
Jones, P.A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484–492 (2012).
Kriaucionis, S. & Heintz, N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324, 929–930 (2009). Authors show that 5hmC is present in high levels in Purkinje cells, suggesting a role for 5hmC in neuronal function.
Tahiliani, M. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930–935 (2009). This paper showed that 5hmC is present in ESCs and is enzymatically produced through TET-catalyzed oxidation of 5mC.
Pfaffeneder, T. et al. The discovery of 5-formylcytosine in embryonic stem cell DNA. Angew. Chem. Int. Ed. Engl. 50, 7008–7012 (2011).
Ito, S. et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300–1303 (2011). In addition, authors quantified 5fC and 5caC using LC-MS/MS in mouse ESCs and tissues.
He, Y.F. et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333, 1303–1307 (2011). This paper revealed the first biochemically validated active DNA demethylation pathway.
Ito, S. et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466, 1129–1133 (2010).
Munzel, M., Globisch, D. & Carell, T. 5-Hydroxymethylcytosine, the sixth base of the genome. Angew. Chem. Int. Ed. Engl. 50, 6460–6468 (2011).
Bhutani, N., Burns, D.M. & Blau, H.M. DNA demethylation dynamics. Cell 146, 866–872 (2011).
Williams, K., Christensen, J. & Helin, K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep. 13, 28–35 (2012).
Branco, M.R., Ficz, G. & Reik, W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat. Rev. Genet. 13, 7–13 (2012).
Wu, H. & Zhang, Y. Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes Dev. 25, 2436–2452 (2011).
Wu, S.C. & Zhang, Y. Active DNA demethylation: many roads lead to Rome. Nat. Rev. Mol. Cell Biol. 11, 607–620 (2010).
Globisch, D. et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS ONE 5, e15367 (2010).
Loenarz, C. & Schofield, C.J. Oxygenase catalyzed 5-methylcytosine hydroxylation. Chem. Biol. 16, 580–583 (2009).
Koh, K.P. et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8, 200–213 (2011).
Williams, K. et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473, 343–348 (2011).
Ficz, G. et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473, 398–402 (2011).
Wu, H. et al. Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev. 25, 679–684 (2011).
Wu, H. et al. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature 473, 389–393 (2011).
Pastor, W.A. et al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473, 394–397 (2011). Authors developed anti-CMS and the GLIB method for genome-wide 5hmC profiling and also demonstrated advantages of the biotin-based enrichment methods.
Maiti, A. & Drohat, A.C. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites. J. Biol. Chem. 286, 35334–35338 (2011).
Zhang, L. et al. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat. Chem. Biol. 8, 328–330 (2012).
Metzker, M.L. Sequencing technologies–the next generation. Nat. Rev. Genet. 11, 31–46 (2010).
Song, C.X. & He, C. The hunt for 5-hydroxymethylcytosine: the sixth base. Epigenomics 3, 521–523 (2011).
Sulewska, A. et al. Detection of DNA methylation in eucaryotic cells. Folia Histochem. Cytobiol. 45, 315–324 (2007).
Fouse, S.D., Nagarajan, R.O. & Costello, J.F. Genome-scale DNA methylation analysis. Epigenomics 2, 105–117 (2010).
Guo, J.U., Su, Y., Zhong, C., Ming, G.-l. & Song, H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145, 423–434 (2011).
Cortellino, S. et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 146, 67–79 (2011).
Nabel, C.S. et al. AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nat. Chem. Biol. 8, 751–758 (2012).
Terragni, J., Bitinaite, J., Zheng, Y. & Pradhan, S. Biochemical characterization of recombinant beta-glucosyltransferase and analysis of global 5-hydroxymethylcytosine in unique genomes. Biochemistry 51, 1009–1019 (2012).
Robertson, A.B. et al. A novel method for the efficient and selective identification of 5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res. 39, e55 (2011).
Grippo, P., Iaccarino, M., Rossi, M. & Scarano, E. Thin-layer chromatography of nucleotides, nucleosides and nucleic acid bases. Biochim. Biophys. Acta 95, 1–7 (1965).
Jin, S.G., Wu, X., Li, A.X. & Pfeifer, G.P. Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res. 39, 5015–5024 (2011).
Li, W. & Liu, M. Distribution of 5-hydroxymethylcytosine in different human tissues. J. Nucleic Acids 2011, 870726 (2011).
Jia, G. et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885–887 (2011). This paper reported FTO as the first known RNA demethylase that mediates m6A demethylation. Authors also quantified m6A by antibody and LC-MS/MS.
Ko, M. et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468, 839–843 (2010).
Szulwach, K.E. et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat. Neurosci. 14, 1607–1616 (2011).
Haffner, M.C. et al. Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers. Oncotarget 2, 627–637 (2011).
Inoue, A. & Zhang, Y. Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science 334, 194 (2011).
Inoue, A., Shen, L., Dai, Q., He, C. & Zhang, Y. Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation development. Cell Res. 21, 1670–1676 (2011).
Höbartner, C. Enzymatic labeling of 5-hydroxymethylcytosine in DNA. Angew. Chem. Int. Ed. Engl. 50, 4268–4270 (2011).
Josse, J. & Kornberg, A. Glucosylation of deoxyribonucleic acid. 3. Alpha and beta-glucosyl transferases from T4-infected Escherichia coli. J. Biol. Chem. 237, 1968–1976 (1962).
Szwagierczak, A., Bultmann, S., Schmidt, C.S., Spada, F. & Leonhardt, H. Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res. 38, e181 (2010).
Singer-Sam, J., LeBon, J.M., Tanguay, R.L. & Riggs, A.D. A quantitative HpaII-PCR assay to measure methylation of DNA from a small number of cells. Nucleic Acids Res. 18, 687 (1990).
Davis, T. & Vaisvila, R. High sensitivity 5-hydroxymethylcytosine detection in Balb/C brain tissue. J. Vis. Exp. 48, e2661 (2011).
Kinney, S.M. et al. Tissue-specific distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes. J. Biol. Chem. 286, 24685–24693 (2011).
Song, C.X., Yu, M., Dai, Q. & He, C. Detection of 5-hydroxymethylcytosine in a combined glycosylation restriction analysis (CGRA) using restriction enzyme Taq(α)I. Bioorg. Med. Chem. Lett. 21, 5075–5077 (2011).
Zheng, Y. et al. A unique family of Mrr-like modification-dependent restriction endonucleases. Nucleic Acids Res. 38, 5527–5534 (2010).
Cohen-Karni, D. et al. The MspJI family of modification-dependent restriction endonucleases for epigenetic studies. Proc. Natl. Acad. Sci. USA 108, 11040–11045 (2011).
Szwagierczak, A. et al. Characterization of PvuRts1I endonuclease as a tool to investigate genomic 5-hydroxymethylcytosine. Nucleic Acids Res. 39, 5149–5156 (2011).
Wang, H. et al. Comparative characterization of the PvuRts1I family of restriction enzymes and their application in mapping genomic 5-hydroxymethylcytosine. Nucleic Acids Res. 39, 9294–9305 (2011).
Xu, S.Y., Corvaglia, A.R., Chan, S.H., Zheng, Y. & Linder, P. A type IV modification-dependent restriction enzyme SauUSI from Staphylococcus aureus subsp. aureus USA300. Nucleic Acids Res. 39, 5597–5610 (2011).
Liutkevičiūtė, Z., Kriukienė, E., Grigaitytė, I., Masevičius, V. & Klimašauskas, S. Methyltransferase-directed derivatization of 5-hydroxymethylcytosine in DNA. Angew. Chem. Int. Ed. Engl. 50, 2090–2093 (2011).
Song, C.X. et al. Detection of 5-hydroxymethylcytosine in DNA by transferring a keto-glucose by using T4 phage β-glucosyltransferase. ChemBioChem 12, 1682–1685 (2011).
Munzel, M. et al. Quantification of the sixth DNA base hydroxymethylcytosine in the brain. Angew. Chem. Int. Ed. Engl. 49, 5375–5377 (2010).
Le, T., Kim, K.P., Fan, G. & Faull, K.F. A sensitive mass spectrometry method for simultaneous quantification of DNA methylation and hydroxymethylation levels in biological samples. Anal. Biochem. 412, 203–209 (2011).
Chan, C.T. et al. A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress. PLoS Genet. 6, e1001247 (2010).
Beck, S. & Rakyan, V.K. The methylome: approaches for global DNA methylation profiling. Trends Genet. 24, 231–237 (2008).
Xu, Y. et al. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol. Cell 42, 451–464 (2011).
Stroud, H., Feng, S., Morey Kinney, S., Pradhan, S. & Jacobsen, S. 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol. 12, R54 (2011).
Serandour, A.A. et al. Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers. Nucleic Acids Res. 40, 8255–8265 (2012).
Matarese, F., Carrillo-de Santa Pau, E. & Stunnenberg, H.G. 5-Hydroxymethylcytosine: a new kid on the epigenetic block? Mol. Syst. Biol. 7, 562 (2011).
Song, C.X. et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat. Biotechnol. 29, 68–72 (2011).This paper reported the first genome-wide 5hmC profiling using hMe-Seal.
Szulwach, K.E. et al. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genet. 7, e1002154 (2011).
Song, C.X. et al. Sensitive and specific single-molecule sequencing of 5-hydroxymethylcytosine. Nat. Methods 9, 75–77 (2012).
Robertson, A.B., Dahl, J.A., Ougland, R. & Klungland, A. Pull-down of 5-hydroxymethylcytosine DNA using JBP1-coated magnetic beads. Nat. Protoc. 7, 340–350 (2012).
Yu, M. et al. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell 149, 1368–1380 (2012). Authors developed TAB-Seq for single-base resolution 5hmC sequencing and performed the first whole-genome mapping of 5hmC sites in mouse and human ESCs.
Korlach, J. & Turner, S.W. Going beyond five bases in DNA sequencing. Curr. Opin. Struct. Biol. 22, 251–261 (2012).
Eid, J. et al. Real-time DNA sequencing from single polymerase molecules. Science 323, 133–138 (2009).
Flusberg, B.A. et al. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat. Methods 7, 461–465 (2010).
Venkatesan, B.M. & Bashir, R. Nanopore sensors for nucleic acid analysis. Nat. Nanotechnol. 6, 615–624 (2011).
Mirsaidov, U. et al. Nanoelectromechanics of methylated DNA in a synthetic nanopore. Biophys. J. 96, L32–L34 (2009).
Wanunu, M. et al. Discrimination of methylcytosine from hydroxymethylcytosine in DNA molecules. J. Am. Chem. Soc. 133, 486–492 (2011).
Wallace, E.V. et al. Identification of epigenetic DNA modifications with a protein nanopore. Chem. Commun. (Camb.) 46, 8195–8197 (2010).
Hayatsu, H. The bisulfite genomic sequencing used in the analysis of epigenetic states, a technique in the emerging environmental genotoxicology research. Mutat. Res. 659, 77–82 (2008).
Booth, M.J. et al. Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution. Science 336, 934–937 (2012).This paper developed oxBS-Seq for single-base resolution 5hmC sequencing and performed 5hmC mapping in CpG islands.
Huang, Y. et al. The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLoS ONE 5, e8888 (2010).
Jin, S.G., Kadam, S. & Pfeifer, G.P. Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res. 38, e125 (2010).
Nestor, C., Ruzov, A., Meehan, R.R. & Dunican, D.S. Enzymatic approaches and bisulfite sequencing cannot distinguish between 5-methylcytosine and 5-hydroxymethylcytosine in DNA. Biotechniques 48, 317–319 (2010).
Grosjean, H. Fine-Tuning of RNA Functions by Modification and Editing (Springer, 2005).
He, C. Grand challenge commentary: RNA epigenetics? Nat. Chem. Biol. 6, 863–865 (2010).
Yi, C. & Pan, T. Cellular dynamics of RNA modification. Acc. Chem. Res. 44, 1380–1388 (2011).
Zhao, X. & Yu, Y.T. Detection and quantitation of RNA base modifications. RNA 10, 996–1002 (2004).
Motorin, Y., Muller, S., Behm-Ansmant, I. & Branlant, C. Identification of modified residues in RNAs by reverse transcription-based methods. Methods Enzymol. 425, 21–53 (2007).
Dai, Q. et al. Identification of recognition residues for ligation-based detection and quantitation of pseudouridine and N6-methyladenosine. Nucleic Acids Res. 35, 6322–6329 (2007).
Saikia, M., Fu, Y., Pavon-Eternod, M., He, C. & Pan, T. Genome-wide analysis of N1-methyl-adenosine modification in human tRNAs. RNA 16, 1317–1327 (2010).
Durairaj, A. & Limbach, P.A. Improving CMC-derivatization of pseudouridine in RNA for mass spectrometric detection. Anal. Chim. Acta 612, 173–181 (2008).
Schaefer, M., Pollex, T., Hanna, K. & Lyko, F. RNA cytosine methylation analysis by bisulfite sequencing. Nucleic Acids Res. 37, e12 (2009).
Motorin, Y., Lyko, F. & Helm, M. 5-methylcytosine in RNA: detection, enzymatic formation and biological functions. Nucleic Acids Res. 38, 1415–1430 (2010).
Squires, J.E. et al. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 40, 5023–5033 (2012).
Sakurai, M., Yano, T., Kawabata, H., Ueda, H. & Suzuki, T. Inosine cyanoethylation identifies A-to-I RNA editing sites in the human transcriptome. Nat. Chem. Biol. 6, 733–740 (2010).
Jepson, J.E. & Reenan, R.A. RNA editing in regulating gene expression in the brain. Biochim. Biophys. Acta 1779, 459–470 (2008).
Li, M. et al. Widespread RNA and DNA sequence differences in the human transcriptome. Science 333, 53–58 (2011).
Pickrell, J.K., Gilad, Y. & Pritchard, J.K. Comment on “Widespread RNA and DNA sequence differences in the human transcriptome”. Science 335, 1302, author reply 1302 (2012).
Lin, W., Piskol, R., Tan, M.H. & Li, J.B. Comment on “Widespread RNA and DNA sequence differences in the human transcriptome”. Science 335, 1302, author reply 1302 (2012).
Kleinman, C.L. & Majewski, J. Comment on “Widespread RNA and DNA sequence differences in the human transcriptome”. Science 335, 1302 author reply 1302 (2012).
Schrider, D.R., Gout, J.F. & Hahn, M.W. Very few RNA and DNA sequence differences in the human transcriptome. PLoS ONE 6, e25842 (2011).
Peng, Z. et al. Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome. Nat. Biotechnol. 30, 253–260 (2012).
Dominissini, D. et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201–206 (2012).This paper reported the dynamic transcriptome-wide m6A distribution by using antibody-based enrichment. It also identified m6A-binding proteins.
Meyer, K.D. et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149, 1635–1646 (2012). This paper reported m6A distribution in HEK cells and mouse brain. It also suggested a correlation between m6A deposition and microRNA binding on mRNA.
Raiber, E.A. et al. Genome-wide distribution of 5-formylcytosine in ES cells is associated with transcription and depends on thymine DNA glycosylase. Genome Biol. 13, R69 (2012).
Münzel, M., Lercher, L., Müller, M. & Carell, T. Chemical discrimination between dC and 5MedC via their hydroxylamine adducts. Nucleic Acids Res. 38, e192 (2010).
Chu, B.C., Wahl, G.M. & Orgel, L.E. Derivatization of unprotected polynucleotides. Nucleic Acids Res. 11, 6513–6529 (1983).
Matsuo, K., Nishikawa, K. & Shindo, M. Stereoselective synthesis of beta-glycosyl esters of cis-cinnamic acid and its derivatives using unprotected glycosyl donors. Tetrahedr. Lett. 52, 5688–5692 (2011).
Horowitz, S., Horowitz, A., Nilsen, T.W., Munns, T.W. & Rottman, F.M. Mapping of N6-methyladenosine residues in bovine prolactin mRNA. Proc. Natl. Acad. Sci. USA 81, 5667–5671 (1984).
Behm-Ansmant, I., Helm, M. & Motorin, Y. Use of specific chemical reagents for detection of modified nucleotides in RNA. J. Nucleic Acids 2011, 408053 (2011).
Moran-Crusio, K. et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20, 11–24 (2011).
Quivoron, C. et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 20, 25–38 (2011).
Iqbal, K., Jin, S.G., Pfeifer, G.P. & Szabo, P.E. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc. Natl. Acad. Sci. USA 108, 3642–3647 (2011).
Wossidlo, M. et al. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat. Commun. 2, 241 (2011).
Gu, T.P. et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477, 606–610 (2011).
Bokar, J.A., Shambaugh, M.E., Polayes, D., Matera, A.G. & Rottman, F.M. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 3, 1233–1247 (1997).
Frauer, C. et al. Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain. PLoS ONE 6, e21306 (2011).
Yildirim, O. et al. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell 147, 1498–1510 (2011).
Penn, N.W., Suwalski, R., O'Riley, C., Bojanowski, K. & Yura, R. The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem. J. 126, 781–790 (1972).
Valinluck, V. et al. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 32, 4100–4108 (2004).
Jin, S.-G. et al. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. Cancer Res. 71, 7360–7365 (2011).
Kudo, Y. et al. Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. Cancer Sci. 103, 670–676 (2012).
Lian, C.G. et al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 150, 1135–1146 (2012).
Schiesser, S. et al. Mechanism and stem-cell activity of 5-carboxycytosine decarboxylation determined by isotope tracing. Angew. Chem. Int. Ed. Engl. 51, 6516–6520 (2012).
Kellinger, M.W. et al. 5-formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription. Nat. Struct. Mol. Biol. 19, 831–833 (2012).
Acknowledgements
This study was supported by US National Institutes of Health (HG006827 to C.H.). We thank S.F. Reichard, for editing the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Song, CX., Yi, C. & He, C. Mapping recently identified nucleotide variants in the genome and transcriptome. Nat Biotechnol 30, 1107–1116 (2012). https://doi.org/10.1038/nbt.2398
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nbt.2398
This article is cited by
-
Modeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet
Genome Biology (2024)
-
RNA modification: mechanisms and therapeutic targets
Molecular Biomedicine (2023)
-
RNA Editing Therapeutics: Advances, Challenges and Perspectives on Combating Heart Disease
Cardiovascular Drugs and Therapy (2023)
-
5-Hydroxymethylcytosine (5hmC) at or near cancer mutation hot spots as potential targets for early cancer detection
BMC Research Notes (2022)
-
A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation
Nature Communications (2020)