Regulation of transposable elements by DNA modifications.
5-Methylcytosine
/ metabolism
Adenosine
/ analogs & derivatives
Animals
Biological Evolution
DNA (Cytosine-5-)-Methyltransferases
/ genetics
DNA Methylation
DNA Transposable Elements
Epigenesis, Genetic
Gene Transfer, Horizontal
Genetic Drift
Humans
Plants
/ genetics
RNA, Small Interfering
/ genetics
Journal
Nature reviews. Genetics
ISSN: 1471-0064
Titre abrégé: Nat Rev Genet
Pays: England
ID NLM: 100962779
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
pubmed:
15
3
2019
medline:
25
7
2019
entrez:
15
3
2019
Statut:
ppublish
Résumé
Maintenance of genome stability requires control over the expression of transposable elements (TEs), whose activity can have substantial deleterious effects on the host. Chemical modification of DNA is a commonly used strategy to achieve this, and it has long been argued that the emergence of 5-methylcytosine (5mC) in many species was driven by the requirement to silence TEs. Potential roles in TE regulation have also been suggested for other DNA modifications, such as N6-methyladenine and oxidation derivatives of 5mC, although the underlying mechanistic relationships are poorly understood. Here, we discuss current evidence implicating DNA modifications and DNA-modifying enzymes in TE regulation across different species.
Identifiants
pubmed: 30867571
doi: 10.1038/s41576-019-0106-6
pii: 10.1038/s41576-019-0106-6
doi:
Substances chimiques
DNA Transposable Elements
0
RNA, Small Interfering
0
5-Methylcytosine
6R795CQT4H
N-methyladenosine
CLE6G00625
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Pagination
417-431Commentaires et corrections
Type : ErratumIn
Références
Gregory, T. R. Coincidence, coevolution, or causation? DNA content, cell size, and the C-value enigma. Biol. Rev. Camb. Philos. Soc. 76, 65–101 (2001).
pubmed: 11325054
doi: 10.1017/S1464793100005595
Jurka, J., Bao, W. & Kojima, K. K. Families of transposable elements, population structure and the origin of species. Biol. Direct 6, 44 (2011).
pubmed: 21929767
pmcid: 3183009
doi: 10.1186/1745-6150-6-44
Sotero-Caio, C. G., Platt, R. N., Suh, A. & Ray, D. A. Evolution and diversity of transposable elements in vertebrate genomes. Genome Biol. Evol. 9, 161–177 (2017).
pubmed: 28158585
pmcid: 5381603
doi: 10.1093/gbe/evw264
Feschotte, C. & Betrán, E. Transposable element domestication as an adaptation to evolutionary conflicts. Trends Genet. 33, 817–831 (2017).
pubmed: 28844698
pmcid: 5659911
doi: 10.1016/j.tig.2017.07.011
Joly-Lopez, Z. & Bureau, T. E. Exaptation of transposable element coding sequences. Curr. Opin. Genet. Dev. 49, 34–42 (2018).
pubmed: 29525543
doi: 10.1016/j.gde.2018.02.011
Chuong, E. B., Elde, N. C. & Feschotte, C. Regulatory activities of transposable elements: from conflicts to benefits. Nat. Rev. Genet. 18, 71–86 (2017).
pubmed: 27867194
doi: 10.1038/nrg.2016.139
Arkhipova, I. R. Neutral theory, transposable elements, and eukaryotic genome evolution. Mol. Biol. Evol. 35, 1332–1337 (2018).
pubmed: 29688526
pmcid: 6455905
doi: 10.1093/molbev/msy083
Gilbert, C. & Feschotte, C. Horizontal acquisition of transposable elements and viral sequences: patterns and consequences. Curr. Opin. Genet. Dev. 49, 15–24 (2018).
pubmed: 29505963
pmcid: 6069605
doi: 10.1016/j.gde.2018.02.007
Wicker, T. et al. A unified classification system for eukaryotic transposable elements. Nat. Rev. Genet. 8, 973–982 (2007). This paper presents a comprehensive description of TE classification and nomenclature, based on a combination of TE sequence structure, phylogeny and mechanisms of transposition.
pubmed: 17984973
doi: 10.1038/nrg2165
Bao, W., Kojima, K. K. & Kohany, O. Repbase Update, a database of repetitive elements in eukaryotic genomes. Mob. DNA 6, 11 (2015).
pubmed: 26045719
pmcid: 4455052
doi: 10.1186/s13100-015-0041-9
Kojima, K. K. Human transposable elements in Repbase: genomic footprints from fish to humans. Mob. DNA 9, 2 (2018).
pubmed: 29308093
pmcid: 5753468
doi: 10.1186/s13100-017-0107-y
Feschotte, C. & Pritham, E. J. DNA transposons and the evolution of eukaryotic genomes. Annu. Rev. Genet. 41, 331–368 (2007).
pubmed: 18076328
pmcid: 2167627
doi: 10.1146/annurev.genet.40.110405.090448
Rodriguez-Terrones, D. & Torres-Padilla, M.-E. Nimble and ready to mingle: transposon outbursts of early development. Trends Genet. 34, 806–820 (2018).
pubmed: 30057183
doi: 10.1016/j.tig.2018.06.006
Tsukahara, S. et al. Bursts of retrotransposition reproduced in Arabidopsis. Nature 461, 423–426 (2009).
pubmed: 19734880
doi: 10.1038/nature08351
Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).
pubmed: 11237011
doi: 10.1038/35057062
Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).
doi: 10.1038/nature01262
Richardson, S. R. et al. Heritable L1 retrotransposition in the mouse primordial germline and early embryo. Genome Res. 27, 1395–1405 (2017).
pubmed: 28483779
pmcid: 5538555
doi: 10.1101/gr.219022.116
Brouha, B. et al. Hot L1s account for the bulk of retrotransposition in the human population. Proc. Natl Acad. Sci. USA 100, 5280–5285 (2003).
pubmed: 12682288
doi: 10.1073/pnas.0831042100
pmcid: 154336
Dewannieux, M., Esnault, C. & Heidmann, T. LINE-mediated retrotransposition of marked Alu sequences. Nat. Genet. 35, 41–48 (2003).
pubmed: 12897783
doi: 10.1038/ng1223
Hancks, D. C. & Kazazian, H. H. Roles for retrotransposon insertions in human disease. Mob. DNA 7, 9 (2016).
pubmed: 27158268
pmcid: 4859970
doi: 10.1186/s13100-016-0065-9
Czech, B. & Hannon, G. J. One loop to rule them all: the ping-pong cycle and piRNA-guided silencing. Trends Biochem. Sci. 41, 324–337 (2016).
pubmed: 26810602
pmcid: 4819955
doi: 10.1016/j.tibs.2015.12.008
Molaro, A. & Malik, H. S. Hide and seek: how chromatin-based pathways silence retroelements in the mammalian germline. Curr. Opin. Genet. Dev. 37, 51–58 (2016).
pubmed: 26821364
pmcid: 4914476
doi: 10.1016/j.gde.2015.12.001
Kim, M. Y. & Zilberman, D. DNA methylation as a system of plant genomic immunity. Trends Plant Sci. 19, 320–326 (2014).
pubmed: 24618094
doi: 10.1016/j.tplants.2014.01.014
Jacobs, F. M. J. et al. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons. Nature 516, 242–245 (2014).
pubmed: 25274305
pmcid: 4268317
doi: 10.1038/nature13760
Imbeault, M., Helleboid, P.-Y. & Trono, D. KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks. Nature 543, 550–554 (2017).
pubmed: 28273063
doi: 10.1038/nature21683
Rowe, H. M. & Trono, D. Dynamic control of endogenous retroviruses during development. Virology 411, 273–287 (2011).
pubmed: 21251689
doi: 10.1016/j.virol.2010.12.007
Dunican, D. S. et al. Lsh regulates LTR retrotransposon repression independently of Dnmt3b function. Genome Biol. 14, R146 (2013).
pubmed: 24367978
pmcid: 4054100
doi: 10.1186/gb-2013-14-12-r146
Zemach, A. et al. The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell 153, 193–205 (2013).
pubmed: 23540698
pmcid: 4035305
doi: 10.1016/j.cell.2013.02.033
Yoder, J. A., Walsh, C. P. & Bestor, T. H. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335–340 (1997).
pubmed: 9260521
doi: 10.1016/S0168-9525(97)01181-5
Ratel, D., Ravanat, J.-L., Berger, F. & Wion, D. N6-methyladenine: the other methylated base of DNA. Bioessays 28, 309–315 (2006).
pubmed: 16479578
pmcid: 2754416
doi: 10.1002/bies.20342
Zhang, G. et al. N6-methyladenine DNA modification in Drosophila. Cell 161, 893–906 (2015). This study describes 6mA dynamics during D. melanogaster embryogenesis and reports a correlation between 6mA demethylation and TE suppression.
pubmed: 25936838
doi: 10.1016/j.cell.2015.04.018
Wu, T. P. et al. DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature 532, 329–333 (2016). This paper is the first to find 6mA in mammalian genomes, identifying both 6mA and its associated demethylase in mouse ESCs, which when removed led to 6mA enrichment at young LINE-1 elements.
pubmed: 27027282
pmcid: 4977844
doi: 10.1038/nature17640
O’Brown, Z. K. & Greer, E. L. N6-methyladenine: a conserved and dynamic DNA mark. Adv. Exp. Med. Biol. 945, 213–246 (2016).
pubmed: 27826841
pmcid: 5291743
doi: 10.1007/978-3-319-43624-1_10
Schiffers, S. et al. Quantitative LC-MS provides no evidence for m6dA or m4dC in the genome of mouse embryonic stem cells and tissues. Angew. Chemie 56, 11268–11271 (2017).
doi: 10.1002/anie.201700424
Lentini, A. et al. A reassessment of DNA-immunoprecipitation-based genomic profiling. Nat. Methods 15, 499–504 (2018).
pubmed: 29941872
doi: 10.1038/s41592-018-0038-7
pmcid: 6625966
Kang, J. et al. Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis. Proc. Natl Acad. Sci. USA 112, E4236–E4245 (2015).
pubmed: 26199412
pmcid: 4534209
la Rica de, L. et al. TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells. Genome Biol. 17, 234 (2016). In this paper, the authors show that TET enzymes demethylate LINE-1 elements in ESCs but also recruit the co-repressor SIN3A to ensure LINE-1 silencing.
doi: 10.1186/s13059-016-1096-8
Zhang, P. et al. L1 retrotransposition is activated by Ten-eleven-translocation protein 1 and repressed by methyl-CpG binding proteins. Nucleus 8, 548–562 (2017).
pubmed: 28524723
pmcid: 5703239
doi: 10.1080/19491034.2017.1330238
Deniz, O., la Rica, de, L., Cheng, K. C. L., Spensberger, D. & Branco, M. R. SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells. Genome Biol. 19, 6 (2018).
pubmed: 29351814
pmcid: 5775534
doi: 10.1186/s13059-017-1376-y
Coluccio, A. et al. Individual retrotransposon integrants are differentially controlled by KZFP/KAP1-dependent histone methylation, DNA methylation and TET-mediated hydroxymethylation in naïve embryonic stem cells. Epigenetics Chromatin 11, 7 (2018).
pubmed: 29482634
pmcid: 6389204
doi: 10.1186/s13072-018-0177-1
Du, J., Johnson, L. M., Jacobsen, S. E. & Patel, D. J. DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol. 16, 519–532 (2015).
pubmed: 26296162
pmcid: 4672940
doi: 10.1038/nrm4043
Schübeler, D. Function and information content of DNA methylation. Nature 517, 321–326 (2015).
pubmed: 25592537
doi: 10.1038/nature14192
Allis, C. D. & Jenuwein, T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17, 487–500 (2016).
doi: 10.1038/nrg.2016.59
pubmed: 27346641
Rasmussen, K. D. & Helin, K. Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 30, 733–750 (2016).
pubmed: 27036965
pmcid: 4826392
doi: 10.1101/gad.276568.115
Wu, X. & Zhang, Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat. Rev. Genet. 18, 517–534 (2017).
pubmed: 28555658
doi: 10.1038/nrg.2017.33
Luo, G.-Z. & He, C. DNA N6-methyladenine in metazoans: functional epigenetic mark or bystander? Nat. Struct. Mol. Biol. 24, 503–506 (2017).
pubmed: 28586322
doi: 10.1038/nsmb.3412
Jeltsch, A. Molecular biology. Phylogeny of methylomes. Science 328, 837–838 (2010).
pubmed: 20466912
doi: 10.1126/science.1190738
Lechner, M. et al. The correlation of genome size and DNA methylation rate in metazoans. Theory Biosci. 132, 47–60 (2013).
pubmed: 23132463
doi: 10.1007/s12064-012-0167-y
Rošic, S. et al. Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity. Nat. Genet. 50, 452–459 (2018).
pubmed: 29459678
pmcid: 5865749
doi: 10.1038/s41588-018-0061-8
Lippman, Z., May, B., Yordan, C., Singer, T. & Martienssen, R. Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification. PLOS Biol. 1, E67 (2003).
pubmed: 14691539
pmcid: 300680
doi: 10.1371/journal.pbio.0000067
Hosaka, A. et al. Evolution of sequence-specific anti-silencing systems in Arabidopsis. Nat. Commun. 8, 2161 (2017).
pubmed: 29255196
pmcid: 5735166
doi: 10.1038/s41467-017-02150-7
Zhou, Y., Cambareri, E. B. & Kinsey, J. A. DNA methylation inhibits expression and transposition of the Neurospora Tad retrotransposon. Mol. Genet. Genomics 265, 748–754 (2001).
pubmed: 11459196
doi: 10.1007/s004380100472
Chernyavskaya, Y. et al. Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling. Development 144, 2925–2939 (2017).
pubmed: 28698226
pmcid: 5592811
Walsh, C. P., Chaillet, J. R. & Bestor, T. H. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet. 20, 116–117 (1998). This study is the first to demonstrate the role of DNA methylation in the silencing of TEs (IAPs) in mouse development.
pubmed: 9771701
doi: 10.1038/2413
Hutnick, L. K. et al. DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation. Hum. Mol. Genet. 18, 2875–2888 (2009).
pubmed: 19433415
pmcid: 2706688
doi: 10.1093/hmg/ddp222
Jackson-Grusby, L. et al. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat. Genet. 27, 31–39 (2001).
pubmed: 11137995
doi: 10.1038/83730
Hutnick, L. K., Huang, X., Loo, T.-C., Ma, Z. & Fan, G. Repression of retrotransposal elements in mouse embryonic stem cells is primarily mediated by a DNA methylation-independent mechanism. J. Biol. Chem. 285, 21082–21091 (2010).
pubmed: 20404320
pmcid: 2898347
doi: 10.1074/jbc.M110.125674
Matsui, T. et al. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature 464, 927–931 (2010).
pubmed: 20164836
doi: 10.1038/nature08858
Karimi, M. M. et al. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell 8, 676–687 (2011). This paper demonstrates that DNA methylation and H3K9me3 are targeted to different loci and that SETDB1-mediated H3K9me3 enrichment contributes to the silencing of certain ERVs in mouse ESCs.
pubmed: 21624812
pmcid: 3857791
doi: 10.1016/j.stem.2011.04.004
Rowe, H. M. et al. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463, 237–240 (2010).
pubmed: 20075919
doi: 10.1038/nature08674
Fasching, L. et al. TRIM28 represses transcription of endogenous retroviruses in neural progenitor cells. Cell Rep. 10, 20–28 (2015).
pubmed: 25543143
doi: 10.1016/j.celrep.2014.12.004
Castro-Diaz, N. et al. Evolutionally dynamic L1 regulation in embryonic stem cells. Genes Dev. 28, 1397–1409 (2014).
pubmed: 24939876
pmcid: 4083085
doi: 10.1101/gad.241661.114
Molaro, A. et al. Two waves of de novo methylation during mouse germ cell development. Genes Dev. 28, 1544–1549 (2014).
pubmed: 25030694
pmcid: 4102761
doi: 10.1101/gad.244350.114
Fadloun, A. et al. Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA. Nat. Struct. Mol. Biol. 20, 332–338 (2013). This study reveals the dynamic nature of TE expression during mouse pre-implantation, underlining a transient expression of LINE-1s during this period.
pubmed: 23353788
doi: 10.1038/nsmb.2495
Aravin, A. A. et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 31, 785–799 (2008).
pubmed: 18922463
pmcid: 2730041
doi: 10.1016/j.molcel.2008.09.003
Hackett, J. A. et al. Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline. Development 139, 3623–3632 (2012).
pubmed: 22949617
pmcid: 3436114
doi: 10.1242/dev.081661
Bourc’his, D. & Bestor, T. H. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431, 96–99 (2004). This seminal paper shows in vivo that DNA methylation is required for transposon silencing during spermatogenesis in mice.
pubmed: 15318244
doi: 10.1038/nature02886
Manakov, S. A. et al. MIWI2 and MILI have differential effects on piRNA biogenesis and DNA methylation. Cell Rep. 12, 1234–1243 (2015).
pubmed: 26279574
pmcid: 4554733
doi: 10.1016/j.celrep.2015.07.036
Barau, J. et al. The DNA methyltransferase DNMT3C protects male germ cells from transposon activity. Science 354, 909–912 (2016). This study discovers DNMT3C, a fourth DNA methyltransferase enzyme that specifically methylates young TEs in the male germ line.
pubmed: 27856912
doi: 10.1126/science.aah5143
Jain, D. et al. rahu is a mutant allele of Dnmt3c, encoding a DNA methyltransferase homolog required for meiosis and transposon repression in the mouse male germline. PLOS Genet. 13, e1006964 (2017).
pubmed: 28854222
pmcid: 5607212
doi: 10.1371/journal.pgen.1006964
Zamudio, N. et al. DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination. Genes Dev. 29, 1256–1270 (2015). In this paper, the authors show that TE silencing during spermatogenesis is required during meiosis owing to an aberrant chromatin structure formed at expressed TE loci, which form meiotic hot spots.
pubmed: 26109049
pmcid: 4495397
doi: 10.1101/gad.257840.114
Murchison, E. P. et al. Critical roles for Dicer in the female germline. Genes Dev. 21, 682–693 (2007).
pubmed: 17369401
pmcid: 1820942
doi: 10.1101/gad.1521307
Tam, O. H. et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453, 534–538 (2008).
pubmed: 18404147
pmcid: 2981145
doi: 10.1038/nature06904
Kabayama, Y. et al. Roles of MIWI, MILI and PLD6 in small RNA regulation in mouse growing oocytes. Nucleic Acids Res. 45, 5387–5398 (2017).
pubmed: 28115634
pmcid: 5435931
Malki, S., van der Heijden, G. W., O’Donnell, K. A., Martin, S. L. & Bortvin, A. A. Role for retrotransposon LINE-1 in fetal oocyte attrition in mice. Dev. Cell 29, 521–533 (2014).
pubmed: 24882376
pmcid: 4056315
doi: 10.1016/j.devcel.2014.04.027
Seisenberger, S. et al. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol. Cell 48, 849–862 (2012). In this paper, the authors describe global DNA methylation dynamics in mouse PGCs featuring DNA methylation-resistant genomic regions, including IAPs, ERV1 and ERVK families.
pubmed: 23219530
pmcid: 3533687
doi: 10.1016/j.molcel.2012.11.001
Lane, N. et al. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35, 88–93 (2003).
pubmed: 12533790
doi: 10.1002/gene.10168
Kobayashi, H. et al. High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice. Genome Res. 23, 616–627 (2013).
pubmed: 23410886
pmcid: 3613579
doi: 10.1101/gr.148023.112
Smith, Z. D. et al. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484, 339–344 (2012).
pubmed: 22456710
pmcid: 3331945
doi: 10.1038/nature10960
Liu, S. et al. Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells. Genes Dev. 28, 2041–2055 (2014). This study identifies SETDB1 as responsible for silencing of DNA demethylation-resistant TEs in PGCs.
pubmed: 25228647
pmcid: 4173156
doi: 10.1101/gad.244848.114
Habibi, E. et al. Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. Cell Stem Cell 13, 360–369 (2013).
doi: 10.1016/j.stem.2013.06.002
pubmed: 23850244
von Meyenn, F. et al. Impairment of DNA methylation maintenance is the main cause of global demethylation in naive embryonic stem cells. Mol. Cell 62, 848–861 (2016). This study shows that replication-dependent passive demethylation is the dominant process during the remodelling of ESC to a naive state. The authors also link H3K9me2 enrichment with UHRF1 recruitment.
doi: 10.1016/j.molcel.2016.04.025
Rothbart, S. B. et al. Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nat. Struct. Mol. Biol. 19, 1155–1160 (2012).
pubmed: 23022729
pmcid: 3492551
doi: 10.1038/nsmb.2391
Liu, X. et al. UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9. Nat. Commun. 4, 1563 (2013).
pubmed: 23463006
doi: 10.1038/ncomms2562
Maenohara, S. et al. Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos. PLOS Genet. 13, e1007042 (2017).
pubmed: 28976982
pmcid: 5643148
doi: 10.1371/journal.pgen.1007042
Walter, M., Teissandier, A., Pérez-Palacios, R. & Bourc’his, D. An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. eLife 5, e11418 (2016).
pubmed: 26814573
pmcid: 4769179
doi: 10.7554/eLife.11418
von Meyenn, F. et al. Comparative principles of DNA methylation reprogramming during human and mouse in vitro primordial germ cell specification. Dev. Cell 39, 104–115 (2016).
doi: 10.1016/j.devcel.2016.09.015
Sharif, J. et al. Activation of endogenous retroviruses in Dnmt1(
pubmed: 27151458
doi: 10.1016/j.stem.2016.03.013
Berrens, R. V. et al. An endosiRNA-based repression mechanism counteracts transposon activation during global DNA demethylation in embryonic stem cells. Cell Stem Cell 21, 694–703 (2017).
pubmed: 29100015
pmcid: 5678422
doi: 10.1016/j.stem.2017.10.004
Gaudet, F. et al. Induction of tumors in mice by genomic hypomethylation. Science 300, 489–492 (2003).
pubmed: 12702876
doi: 10.1126/science.1083558
Iskow, R. C. et al. Natural mutagenesis of human genomes by endogenous retrotransposons. Cell 141, 1253–1261 (2010).
pubmed: 20603005
pmcid: 2943760
doi: 10.1016/j.cell.2010.05.020
Schauer, S. N. et al. L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis. Genome Res. 28, 639–653 (2018).
pubmed: 29643204
pmcid: 5932605
doi: 10.1101/gr.226993.117
Nguyen, T. H. M. et al. L1 retrotransposon heterogeneity in ovarian tumor cell evolution. Cell Rep. 23, 3730–3740 (2018).
pubmed: 29949758
doi: 10.1016/j.celrep.2018.05.090
Rodic, N. et al. Long interspersed element-1 protein expression is a hallmark of many human cancers. Am. J. Pathol. 184, 1280–1286 (2014).
pubmed: 24607009
pmcid: 4005969
doi: 10.1016/j.ajpath.2014.01.007
Lee, E. et al. Landscape of somatic retrotransposition in human cancers. Science 337, 967–971 (2012). This study provides a detailed overview of somatic TE retrotransposition activity in different types of cancer.
pubmed: 22745252
pmcid: 3656569
doi: 10.1126/science.1222077
Burns, K. H. Transposable elements in cancer. Nat. Rev. Genet. 17, 415–424 (2017).
Babaian, A. & Mager, D. L. Endogenous retroviral promoter exaptation in human cancer. Mob. DNA 7, 24 (2016).
pubmed: 27980689
pmcid: 5134097
doi: 10.1186/s13100-016-0080-x
Weber, B., Kimhi, S., Howard, G., Eden, A. & Lyko, F. Demethylation of a LINE-1 antisense promoter in the cMet locus impairs Met signalling through induction of illegitimate transcription. Oncogene 29, 5775–5784 (2010).
pubmed: 20562909
doi: 10.1038/onc.2010.227
Cruickshanks, H. A. & Tufarelli, C. Isolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter. Genomics 94, 397–406 (2009).
pubmed: 19720139
doi: 10.1016/j.ygeno.2009.08.013
Brocks, D. et al. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat. Genet. 49, 1052–1060 (2017).
pubmed: 28604729
pmcid: 6005702
doi: 10.1038/ng.3889
Cuellar, T. L. et al. Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia. J. Cell Biol. 216, 3535–3549 (2017).
pubmed: 28887438
pmcid: 5674883
doi: 10.1083/jcb.201612160
Sheng, W. et al. LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell 174, 549–563 (2018).
pubmed: 29937226
doi: 10.1016/j.cell.2018.05.052
pmcid: 6063761
Roulois, D. et al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162, 961–973 (2015). This study is the first to report that tumour-suppressive strategies of DNA-demethylating agents are actually via an interferon response associated with ERV activation.
pubmed: 26317465
pmcid: 4843502
doi: 10.1016/j.cell.2015.07.056
Chiappinelli, K. B. et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162, 974–986 (2015).
pubmed: 26317466
pmcid: 4556003
doi: 10.1016/j.cell.2015.07.011
Ohtani, H., Liu, M., Zhou, W., Liang, G. & Jones, P. A. Switching roles for DNA and histone methylation depend on evolutionary ages of human endogenous retroviruses. Genome Res. 28, 1147–1157 (2018).
pubmed: 29970451
pmcid: 6071641
doi: 10.1101/gr.234229.118
Li, Y., Kumar, S. & Qian, W. Active DNA demethylation: mechanism and role in plant development. Plant Cell Rep. 37, 77–85 (2018).
pubmed: 29026973
doi: 10.1007/s00299-017-2215-z
Wyatt, G. R. & Cohen, S. S. The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine. Biochem. J. 55, 774–782 (1953).
pubmed: 13115372
pmcid: 1269533
doi: 10.1042/bj0550774
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).
pubmed: 4538516
pmcid: 1178489
doi: 10.1042/bj1260781
Tahiliani, M. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930–935 (2009). This study discovers that TET proteins catalyse the conversion of 5mC to 5hmC by an oxidation reaction.
pubmed: 19372391
pmcid: 2715015
doi: 10.1126/science.1170116
Ito, S. et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300–1303 (2011).
pubmed: 21778364
pmcid: 3495246
doi: 10.1126/science.1210597
He, Y.-F. et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333, 1303–1307 (2011).
pubmed: 21817016
pmcid: 3462231
doi: 10.1126/science.1210944
Inoue, A. & Zhang, Y. Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science 334, 194–194 (2011).
pubmed: 21940858
pmcid: 3799877
doi: 10.1126/science.1212483
Hashimoto, H. et al. Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation. Nucleic Acids Res. 40, 4841–4849 (2012).
pubmed: 22362737
pmcid: 3367191
doi: 10.1093/nar/gks155
Globisch, D. et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLOS ONE 5, e15367 (2010).
pubmed: 21203455
pmcid: 3009720
doi: 10.1371/journal.pone.0015367
Almeida, R. D. et al. Semi-quantitative immunohistochemical detection of 5-hydroxymethyl-cytosine reveals conservation of its tissue distribution between amphibians and mammals. Epigenetics 7, 137–140 (2012).
pubmed: 22395462
pmcid: 3335906
doi: 10.4161/epi.7.2.18949
Kamstra, J. H., Løken, M., Aleström, P. & Legler, J. Dynamics of DNA hydroxymethylation in zebrafish. Zebrafish 12, 230–237 (2015).
pubmed: 25751297
doi: 10.1089/zeb.2014.1033
Upton, K. R. et al. Ubiquitous L1 mosaicism in hippocampal neurons. Cell 161, 228–239 (2015).
pubmed: 25860606
pmcid: 4398972
doi: 10.1016/j.cell.2015.03.026
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).
pubmed: 20685817
pmcid: 2965258
doi: 10.1093/nar/gkq684
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).
pubmed: 22052461
pmcid: 3242933
doi: 10.1158/0008-5472.CAN-11-2023
Pfaffeneder, T. et al. The discovery of 5-formylcytosine in embryonic stem cell DNA. Angew. Chemie 50, 7008–7012 (2011).
doi: 10.1002/anie.201103899
Iyer, L. M., Tahiliani, M., Rao, A. & Aravind, L. Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids. Cell Cycle 8, 1698–1710 (2009).
pubmed: 19411852
doi: 10.4161/cc.8.11.8580
Iyer, L. M. et al. Lineage-specific expansions of TET/JBP genes and a new class of DNA transposons shape fungal genomic and epigenetic landscapes. Proc. Natl Acad. Sci. USA 111, 1676–1683 (2014).
pubmed: 24398522
doi: 10.1073/pnas.1321818111
pmcid: 3918813
Chavez, L. et al. Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea. Proc. Natl Acad. Sci. USA 111, E5149–E5158 (2014).
pubmed: 25406324
doi: 10.1073/pnas.1419513111
pmcid: 4260599
Wang, X.-L. et al. Genome-wide mapping of 5-hydroxymethylcytosine in three rice cultivars reveals its preferential localization in transcriptionally silent transposable element genes. J. Exp. Bot. 66, 6651–6663 (2015).
pubmed: 26272901
pmcid: 4715260
doi: 10.1093/jxb/erv372
Ficz, G. et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473, 398–402 (2011).
pubmed: 21460836
doi: 10.1038/nature10008
Booth, M. J. et al. Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution. Science 336, 934–937 (2012).
pubmed: 22539555
doi: 10.1126/science.1220671
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).
pubmed: 22124233
pmcid: 3357997
doi: 10.1038/cr.2011.189
Gu, T.-P. et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477, 606–610 (2011).
doi: 10.1038/nature10443
pubmed: 21892189
Amouroux, R. et al. De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nat. Cell Biol. 18, 225–233 (2016).
pubmed: 26751286
pmcid: 4765106
doi: 10.1038/ncb3296
Shen, L. et al. Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes. Cell Stem Cell 15, 459–470 (2014).
pubmed: 25280220
pmcid: 4201500
doi: 10.1016/j.stem.2014.09.002
Kim, S.-H. et al. Differential DNA methylation reprogramming of various repetitive sequences in mouse preimplantation embryos. Biochem. Biophys. Res. Commun. 324, 58–63 (2004).
pubmed: 15464982
doi: 10.1016/j.bbrc.2004.09.023
Inoue, A., Matoba, S. & Zhang, Y. Transcriptional activation of transposable elements in mouse zygotes is independent of Tet3-mediated 5-methylcytosine oxidation. Cell Res. 22, 1640–1649 (2012).
pubmed: 23184059
pmcid: 3515759
doi: 10.1038/cr.2012.160
Vella, P. et al. Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol. Cell 49, 645–656 (2013).
pubmed: 23352454
doi: 10.1016/j.molcel.2012.12.019
Chen, Q., Chen, Y., Bian, C., Fujiki, R. & Yu, X. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature 493, 561–564 (2013).
pubmed: 23222540
doi: 10.1038/nature11742
Deplus, R. et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 32, 645–655 (2013).
pubmed: 23353889
pmcid: 3590984
doi: 10.1038/emboj.2012.357
Williams, K. et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473, 343–348 (2011).
pubmed: 21490601
pmcid: 3408592
doi: 10.1038/nature10066
Neri, F. et al. Genome-wide analysis identifies a functional association of Tet1 and Polycomb repressive complex 2 in mouse embryonic stem cells. Genome Biol. 14, R91 (2013).
pubmed: 23987249
pmcid: 4053938
doi: 10.1186/gb-2013-14-8-r91
Guallar, D. et al. RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nat. Genet. 30, 733 (2018).
Leung, D. et al. Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1. Proc. Natl Acad. Sci. USA 111, 6690–6695 (2014).
pubmed: 24757056
doi: 10.1073/pnas.1322273111
pmcid: 4020067
Bachman, M. et al. 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat. Chem. 6, 1049–1055 (2014).
pubmed: 25411882
pmcid: 4382525
doi: 10.1038/nchem.2064
Bachman, M. et al. 5-Formylcytosine can be a stable DNA modification in mammals. Nat. Chem. Biol. 11, 555–557 (2015).
pubmed: 26098680
pmcid: 5486442
doi: 10.1038/nchembio.1848
Hashimoto, H. et al. Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence. Genes Dev. 28, 2304–2313 (2014).
pubmed: 25258363
pmcid: 4201290
doi: 10.1101/gad.250746.114
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).
pubmed: 22820989
pmcid: 3414690
doi: 10.1038/nsmb.2346
Iurlaro, M. et al. A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation. Genome Biol. 14, R119 (2013).
pubmed: 24156278
pmcid: 4014808
doi: 10.1186/gb-2013-14-10-r119
Spruijt, C. G. et al. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Cell 152, 1146–1159 (2013).
doi: 10.1016/j.cell.2013.02.004
pubmed: 23434322
Xiong, J. et al. Cooperative action between SALL4A and TET proteins in stepwise oxidation of 5-methylcytosine. Mol. Cell 64, 913–925 (2016).
pubmed: 27840027
doi: 10.1016/j.molcel.2016.10.013
Fu, Y. et al. N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas. Cell 161, 879–892 (2015).
pubmed: 25936837
pmcid: 4427561
doi: 10.1016/j.cell.2015.04.010
Greer, E. L. et al. DNA methylation on N6-adenine in C. elegans. Cell 161, 868–878 (2015).
pubmed: 25936839
pmcid: 4427530
doi: 10.1016/j.cell.2015.04.005
Koziol, M. J. et al. Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat. Struct. Mol. Biol. 23, 24–30 (2016).
pubmed: 26689968
doi: 10.1038/nsmb.3145
Xiao, C.-L. et al. N6-methyladenine DNA modification in the human genome. Mol. Cell 71, 306–318 (2018).
pubmed: 30017583
doi: 10.1016/j.molcel.2018.06.015
Sánchez-Romero, M. A., Cota, I. & Casadesús, J. DNA methylation in bacteria: from the methyl group to the methylome. Curr. Opin. Microbiol. 25, 9–16 (2015).
pubmed: 25818841
doi: 10.1016/j.mib.2015.03.004
Roberts, D., Hoopes, B. C., McClure, W. R. & Kleckner, N. IS10 transposition is regulated by DNA adenine methylation. Cell 43, 117–130 (1985). Dam -mutant E. coli are used to show that 6mA loss results in increased transcription of the IS10 transposon and that this leads to transposition.
pubmed: 3000598
doi: 10.1016/0092-8674(85)90017-0
Wang, Y., Chen, X., Sheng, Y., Liu, Y. & Gao, S. N6-adenine DNA methylation is associated with the linker DNA of H2A. Z-containing well-positioned nucleosomes in Pol II-transcribed genes in Tetrahymena. Nucleic Acids Res. 45, 11594–11606 (2017).
pubmed: 29036602
pmcid: 5714169
doi: 10.1093/nar/gkx883
Chen, H. et al. Phytophthora methylomes are modulated by 6 mA methyltransferases and associated with adaptive genome regions. Genome Biol. 19, 181 (2018).
pubmed: 30382931
pmcid: 6211444
doi: 10.1186/s13059-018-1564-4
Liang, Z. et al. DNA N6-adenine methylation in Arabidopsis thaliana. Dev. Cell 45, 406–416 (2018).
pubmed: 29656930
doi: 10.1016/j.devcel.2018.03.012
Liu, J. et al. Abundant DNA 6 mA methylation during early embryogenesis of zebrafish and pig. Nat. Commun. 7, 13052 (2016).
pubmed: 27713410
pmcid: 5059759
doi: 10.1038/ncomms13052
Yao, B. et al. DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress. Nat. Commun. 8, 1122 (2017).
pubmed: 29066820
pmcid: 5654764
doi: 10.1038/s41467-017-01195-y
Zhu, S. et al. Mapping and characterizing N6-methyladenine in eukaryotic genomes using single-molecule real-time sequencing. Genome Res. 28, 1067–1078 (2018).
pubmed: 29764913
pmcid: 6028124
doi: 10.1101/gr.231068.117
Xie, Q. et al. N6-methyladenine DNA modification in glioblastoma. Cell 175, 1228–1243 (2018).
pubmed: 30392959
doi: 10.1016/j.cell.2018.10.006
pmcid: 6433469
Mondo, S. J. et al. Widespread adenine N6-methylation of active genes in fungi. Nat. Genet. 49, 964–968 (2017).
pubmed: 28481340
doi: 10.1038/ng.3859
Brocken, D. J. W., Tark-Dame, M. & Dame, R. T. dCas9: a versatile tool for epigenome editing. Curr. Issues Mol. Biol. 26, 15–32 (2018).
pubmed: 28879853
doi: 10.21775/cimb.026.015
Machnicka, M. A. et al. MODOMICS: a database of RNA modification pathways—2013 update. Nucleic Acids Res. 41, D262–D267 (2013).
pubmed: 23118484
doi: 10.1093/nar/gks1007
Zhao, B. S., Roundtree, I. A. & He, C. Post-transcriptional gene regulation by mRNA modifications. Nat. Rev. Mol. Cell Biol. 18, 31–42 (2017).
pubmed: 27808276
doi: 10.1038/nrm.2016.132
Wan, Y. et al. Transcriptome-wide high-throughput deep m(6)A-seq reveals unique differential m(6)A methylation patterns between three organs in Arabidopsis thaliana. Genome Biol. 16, 272 (2015).
pubmed: 26667818
pmcid: 4714525
doi: 10.1186/s13059-015-0839-2
Zhang, Z. & Xing, Y. CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome. Nucleic Acids Res. 45, 9260–9271 (2017).
pubmed: 28934506
pmcid: 5766199
doi: 10.1093/nar/gkx646
Huang, L., Ashraf, S., Wang, J. & Lilley, D. M. Control of box C/D snoRNP assembly by N6-methylation of adenine. EMBO Rep. 18, 1631–1645 (2017).
pubmed: 28623187
pmcid: 5579392
doi: 10.15252/embr.201743967
Zhou, C. et al. Genome-wide maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAs. Cell Rep. 20, 2262–2276 (2017).
pubmed: 28854373
pmcid: 5705222
doi: 10.1016/j.celrep.2017.08.027
Horwich, M. D. et al. The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr. Biol. 17, 1265–1272 (2007).
pubmed: 17604629
doi: 10.1016/j.cub.2007.06.030
Saito, K. et al. Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi- interacting RNAs at their 3′ ends. Genes Dev. 21, 1603–1608 (2007).
pubmed: 17606638
pmcid: 1899469
doi: 10.1101/gad.1563607
Kamminga, L. M. et al. Hen1 is required for oocyte development and piRNA stability in zebrafish. EMBO J. 29, 3688–3700 (2010).
pubmed: 20859253
pmcid: 2982757
doi: 10.1038/emboj.2010.233
Jackman, J. E. & Alfonzo, J. D. Transfer RNA modifications: nature’s combinatorial chemistry playground. Wiley Interdiscip. Rev. RNA 4, 35–48 (2013).
pubmed: 23139145
doi: 10.1002/wrna.1144
Chou, H.-J., Donnard, E., Gustafsson, H. T., Garber, M. & Rando, O. J. Transcriptome-wide analysis of roles for tRNA modifications in translational regulation. Mol. Cell 68, 978–992 (2017).
Phalke, S. et al. Retrotransposon silencing and telomere integrity in somatic cells of Drosophila depends on the cytosine-5 methyltransferase DNMT2. Nat. Genet. 41, 696–702 (2009).
pubmed: 19412177
doi: 10.1038/ng.360
Kuhlmann, M. et al. Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi. Nucleic Acids Res. 33, 6405–6417 (2005).
pubmed: 16282589
pmcid: 1283529
doi: 10.1093/nar/gki952
Raddatz, G. et al. Dnmt2-dependent methylomes lack defined DNA methylation patterns. Proc. Natl Acad. Sci. USA 110, 8627–8631 (2013).
pubmed: 23641003
doi: 10.1073/pnas.1306723110
pmcid: 3666705
Genenncher, B. et al. Mutations in cytosine-5 tRNA methyltransferases impact mobile element expression and genome stability at specific DNA repeats. Cell Rep. 22, 1861–1874 (2018).
pubmed: 29444437
doi: 10.1016/j.celrep.2018.01.061
Ibarra, C. A. et al. Active DNA demethylation in plant companion cells reinforces transposon methylation in gametes. Science 337, 1360–1364 (2012). This paper provides genome-wide evidence that flowering plants use companion cells to protect their gametes from harmful transposition.
pubmed: 22984074
pmcid: 4034762
doi: 10.1126/science.1224839
Rowe, H. M. et al. De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET. Development 140, 519–529 (2013).
pubmed: 23293284
doi: 10.1242/dev.087585