Advertisement

RNome and Chromatin Dynamics

  • Mansi Arora
  • Deepak Kaul
Chapter

Abstract

Epigenetic changes are central to the regulation of gene expression in eukaryotes. Different environmental and developmental cues bring about a change in total RNA pool that dictates cellular responses without changing the original genetic information. Interestingly, the epigenetic machinery is itself regulated by several non-coding RNAs (ncRNAs). Adding to this intricate network are the recently discovered RNA modifications. Termed as “epitranscriptomics,” these RNA modifications significantly impact RNA localization and function by changing its structure or ability to bind with different biochemical partners. This chapter explores different epigenetic mechanisms (such as DNA and histone modifications and chromatin remodeling), reciprocal relationship between ncRNAs, and chromatic dynamics as well as RNA modifications and their role in gene regulation.

Keywords

Chromatin modifications Epigenetics Epitranscriptomics ncRNAs RNA modifications 

References

  1. Alarcón CR, Goodarzi H, Lee H et al (2015a) HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell 162:1299–1308.  https://doi.org/10.1016/j.cell.2015.08.011CrossRefPubMedPubMedCentralGoogle Scholar
  2. Alarcón CR, Lee H, Goodarzi H et al (2015b) N6-methyladenosine marks primary microRNAs for processing. Nature 519:482–485.  https://doi.org/10.1038/nature14281CrossRefPubMedPubMedCentralGoogle Scholar
  3. Angrand P-O, Vennin C, Le Bourhis X, Adriaenssens E (2015) The role of long non-coding RNAs in genome formatting and expression. Front Genet 6:165.  https://doi.org/10.3389/fgene.2015.00165CrossRefPubMedPubMedCentralGoogle Scholar
  4. Arab K, Park YJ, Lindroth AM et al (2014) Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol Cell 55:604–614.  https://doi.org/10.1016/j.molcel.2014.06.031CrossRefPubMedGoogle Scholar
  5. Avesson L, Barry G (2014) The emerging role of RNA and DNA editing in cancer. Biochim Biophys Acta 1845:308–316.  https://doi.org/10.1016/j.bbcan.2014.03.001CrossRefPubMedGoogle Scholar
  6. Bao X, Wu H, Zhu X et al (2015) The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters. Cell Res 25:80–92.  https://doi.org/10.1038/cr.2014.165CrossRefPubMedGoogle Scholar
  7. Barski A, Cuddapah S, Cui K et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837.  https://doi.org/10.1016/j.cell.2007.05.009CrossRefPubMedPubMedCentralGoogle Scholar
  8. Batista PJ, Molinie B, Wang J et al (2014) m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15:707–719.  https://doi.org/10.1016/j.stem.2014.09.019CrossRefPubMedPubMedCentralGoogle Scholar
  9. Bernstein E, Allis CD (2005) RNA meets chromatin. Genes Dev 19:1635–1655.  https://doi.org/10.1101/gad.1324305CrossRefPubMedGoogle Scholar
  10. Black JC, Van Rechem C, Whetstine JR (2012) Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell 48:491–507.  https://doi.org/10.1016/j.molcel.2012.11.006CrossRefPubMedGoogle Scholar
  11. Brait M, Sidransky D (2011) Cancer epigenetics: above and beyond. Toxicol Mech Methods 21:275–288.  https://doi.org/10.3109/15376516.2011.562671CrossRefPubMedPubMedCentralGoogle Scholar
  12. Britten RJ, Davidson EH (1969) Gene regulation for higher cells: a theory. Science 165:349–357CrossRefGoogle Scholar
  13. Cantara WA, Crain PF, Rozenski J et al (2011) The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Res 39:D195–D201.  https://doi.org/10.1093/nar/gkq1028CrossRefPubMedGoogle Scholar
  14. Cao J, Yan Q (2012) Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front Oncol 2:26.  https://doi.org/10.3389/fonc.2012.00026CrossRefPubMedPubMedCentralGoogle Scholar
  15. Chalei V, Sansom SN, Kong L et al (2014) The long non-coding RNA Dali is an epigenetic regulator of neural differentiation. eLife 3:e04530.  https://doi.org/10.7554/eLife.04530CrossRefPubMedPubMedCentralGoogle Scholar
  16. Chang B, Chen Y, Zhao Y, Bruick RK (2007) JMJD6 is a histone arginine demethylase. Science 318:444–447.  https://doi.org/10.1126/science.1145801CrossRefPubMedGoogle Scholar
  17. Chang H-M, Triboulet R, Thornton JE, Gregory RI (2013) A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway. Nature 497:244–248.  https://doi.org/10.1038/nature12119CrossRefPubMedPubMedCentralGoogle Scholar
  18. Chen T, Hao Y-J, Zhang Y et al (2015) m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 16:289–301.  https://doi.org/10.1016/j.stem.2015.01.016CrossRefPubMedGoogle Scholar
  19. Clapier CR, Cairns BR (2009) The biology of chromatin remodeling complexes. Annu Rev Biochem 78:273–304.  https://doi.org/10.1146/annurev.biochem.77.062706.153223CrossRefPubMedGoogle Scholar
  20. Clark MB, Choudhary A, Smith MA et al (2013) The dark matter rises: the expanding world of regulatory RNAs. Essays Biochem 54:1–16.  https://doi.org/10.1042/bse0540001CrossRefPubMedGoogle Scholar
  21. Cohn WE (1951) Some results of the applications of ion-exchange chromatography to nucleic acid chemistry. J Cell Physiol Suppl 38:21–40CrossRefGoogle Scholar
  22. Colquitt BM, Allen WE, Barnea G, Lomvardas S (2013) Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity. Proc Natl Acad Sci U S A 110:14682–14687.  https://doi.org/10.1073/pnas.1302759110CrossRefPubMedPubMedCentralGoogle Scholar
  23. Davis FF, Allen FW (1957) Ribonucleic acids from yeast which contain a fifth nucleotide. J Biol Chem 227:907–915Google Scholar
  24. Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150:12–27.  https://doi.org/10.1016/j.cell.2012.06.013CrossRefPubMedGoogle Scholar
  25. Desrosiers R, Friderici K, Rottman F (1974) Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci U S A 71:3971–3975CrossRefGoogle Scholar
  26. Di Lorenzo A, Bedford MT (2011) Histone arginine methylation. FEBS Lett 585:2024–2031.  https://doi.org/10.1016/j.febslet.2010.11.010CrossRefPubMedGoogle Scholar
  27. Di Ruscio A, Ebralidze AK, Benoukraf T et al (2013) DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 503:371–376.  https://doi.org/10.1038/nature12598CrossRefPubMedPubMedCentralGoogle Scholar
  28. Dillon SC, Zhang X, Trievel RC, Cheng X (2005) The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol 6:227.  https://doi.org/10.1186/gb-2005-6-8-227CrossRefPubMedPubMedCentralGoogle Scholar
  29. Dominissini D, Moshitch-Moshkovitz S, Amariglio N, Rechavi G (2011) Adenosine-to-inosine RNA editing meets cancer. Carcinogenesis 32:1569–1577.  https://doi.org/10.1093/carcin/bgr124CrossRefPubMedGoogle Scholar
  30. Dominissini D, Moshitch-Moshkovitz S, Schwartz S et al (2012) Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485:201–206.  https://doi.org/10.1038/nature11112CrossRefPubMedGoogle Scholar
  31. Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S et al (2016) The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. Nature 530:441–446.  https://doi.org/10.1038/nature16998CrossRefPubMedPubMedCentralGoogle Scholar
  32. Fabbri M, Garzon R, Cimmino A et al (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 104:15805–15810.  https://doi.org/10.1073/pnas.0707628104CrossRefPubMedPubMedCentralGoogle Scholar
  33. Faehnle CR, Walleshauser J, Joshua-Tor L (2014) Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway. Nature 514:252–256.  https://doi.org/10.1038/nature13553CrossRefPubMedPubMedCentralGoogle Scholar
  34. Frank F, Sonenberg N, Nagar B (2010) Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2. Nature 465:818–822.  https://doi.org/10.1038/nature09039CrossRefPubMedGoogle Scholar
  35. Frye M, Jaffrey SR, Pan T et al (2016) RNA modifications: what have we learned and where are we headed? Nat Rev Genet 17:365–372.  https://doi.org/10.1038/nrg.2016.47CrossRefPubMedGoogle Scholar
  36. Fu X, Jin L, Wang X et al (2013a) MicroRNA-26a targets ten eleven translocation enzymes and is regulated during pancreatic cell differentiation. Proc Natl Acad Sci U S A 110:17892–17897.  https://doi.org/10.1073/pnas.1317397110CrossRefPubMedPubMedCentralGoogle Scholar
  37. Fu Y, Jia G, Pang X et al (2013b) FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat Commun 4:1798.  https://doi.org/10.1038/ncomms2822CrossRefPubMedPubMedCentralGoogle Scholar
  38. Garzon R, Liu S, Fabbri M et al (2009) MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113:6411–6418.  https://doi.org/10.1182/blood-2008-07-170589CrossRefPubMedPubMedCentralGoogle Scholar
  39. Geisler S, Coller J (2013) RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol 14:699–712.  https://doi.org/10.1038/nrm3679CrossRefPubMedPubMedCentralGoogle Scholar
  40. Geula S, Moshitch-Moshkovitz S, Dominissini D et al (2015) Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347:1002–1006.  https://doi.org/10.1126/science.1261417CrossRefPubMedGoogle Scholar
  41. Gilbert WV, Bell TA, Schaening C (2016) Messenger RNA modifications: form, distribution, and function. Science 352:1408–1412.  https://doi.org/10.1126/science.aad8711CrossRefPubMedPubMedCentralGoogle Scholar
  42. Hagan JP, Piskounova E, Gregory RI (2009) Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol 16:1021–1025.  https://doi.org/10.1038/nsmb.1676CrossRefPubMedPubMedCentralGoogle Scholar
  43. Hayashi-Takanaka Y, Yamagata K, Nozaki N, Kimura H (2009) Visualizing histone modifications in living cells: spatiotemporal dynamics of H3 phosphorylation during interphase. J Cell Biol 187:781–790.  https://doi.org/10.1083/jcb.200904137CrossRefPubMedPubMedCentralGoogle Scholar
  44. 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.1210944CrossRefPubMedPubMedCentralGoogle Scholar
  45. Heintzman ND, Hon GC, Hawkins RD et al (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459:108–112.  https://doi.org/10.1038/nature07829CrossRefPubMedPubMedCentralGoogle Scholar
  46. Heo I, Joo C, Kim Y-K et al (2009) TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell 138:696–708.  https://doi.org/10.1016/j.cell.2009.08.002CrossRefPubMedGoogle Scholar
  47. Heo I, Ha M, Lim J et al (2012) Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs. Cell 151:521–532.  https://doi.org/10.1016/j.cell.2012.09.022CrossRefPubMedGoogle Scholar
  48. Hermann A, Goyal R, Jeltsch A (2004) The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J Biol Chem 279:48350–48359.  https://doi.org/10.1074/jbc.M403427200CrossRefPubMedGoogle Scholar
  49. Hirose T, Virnicchi G, Tanigawa A et al (2014) NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol Biol Cell 25:169–183.  https://doi.org/10.1091/mbc.E13-09-0558CrossRefPubMedPubMedCentralGoogle Scholar
  50. 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.1210597CrossRefPubMedPubMedCentralGoogle Scholar
  51. Jia G, Fu Y, Zhao X et al (2011) N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 7:885–887.  https://doi.org/10.1038/nchembio.687CrossRefPubMedPubMedCentralGoogle Scholar
  52. Jiao AL, Slack FJ (2014) RNA-mediated gene activation. Epigenetics 9:27–36.  https://doi.org/10.4161/epi.26942CrossRefPubMedGoogle Scholar
  53. Jin C, Zang C, Wei G et al (2009) H3.3/H2A.Z double variant-containing nucleosomes mark “nucleosome-free regions” of active promoters and other regulatory regions. Nat Genet 41:941–945.  https://doi.org/10.1038/ng.409CrossRefPubMedPubMedCentralGoogle Scholar
  54. Karijolich J, Yu Y-T (2015) The new era of RNA modification. RNA N Y N 21:659–660.  https://doi.org/10.1261/rna.049650.115CrossRefGoogle Scholar
  55. Kawamata T, Yoda M, Tomari Y (2011) Multilayer checkpoints for microRNA authenticity during RISC assembly. EMBO Rep 12:944–949.  https://doi.org/10.1038/embor.2011.128CrossRefPubMedPubMedCentralGoogle Scholar
  56. Ke S, Alemu EA, Mertens C et al (2015) A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation. Genes Dev 29:2037–2053.  https://doi.org/10.1101/gad.269415.115CrossRefPubMedPubMedCentralGoogle Scholar
  57. Kelly TK, Miranda TB, Liang G et al (2010) H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes. Mol Cell 39:901–911.  https://doi.org/10.1016/j.molcel.2010.08.026CrossRefPubMedPubMedCentralGoogle Scholar
  58. Khorkova O, Hsiao J, Wahlestedt C (2015) Basic biology and therapeutic implications of lncRNA. Adv Drug Deliv Rev 87:15–24.  https://doi.org/10.1016/j.addr.2015.05.012CrossRefPubMedPubMedCentralGoogle Scholar
  59. Kim B, Ha M, Loeff L et al (2015) TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms. EMBO J 34:1801–1815.  https://doi.org/10.15252/embj.201590931CrossRefPubMedPubMedCentralGoogle Scholar
  60. Kishikawa S, Murata T, Kimura H et al (2002) Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins. Eur J Biochem 269:2961–2970CrossRefGoogle Scholar
  61. Kooistra SM, Helin K (2012) Molecular mechanisms and potential functions of histone demethylases. Nat Rev Mol Cell Biol 13:297–311.  https://doi.org/10.1038/nrm3327CrossRefPubMedGoogle Scholar
  62. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705.  https://doi.org/10.1016/j.cell.2007.02.005CrossRefPubMedGoogle Scholar
  63. Kung JTY, Colognori D, Lee JT (2013) Long noncoding RNAs: past, present, and future. Genetics 193:651–669.  https://doi.org/10.1534/genetics.112.146704CrossRefPubMedPubMedCentralGoogle Scholar
  64. Längst G, Manelyte L (2015) Chromatin remodelers: from function to dysfunction. Genes 6:299–324.  https://doi.org/10.3390/genes6020299CrossRefPubMedPubMedCentralGoogle Scholar
  65. Lee JT (2012) Epigenetic regulation by long noncoding RNAs. Science 338:1435–1439.  https://doi.org/10.1126/science.1231776CrossRefPubMedGoogle Scholar
  66. Lee J-S, Smith E, Shilatifard A (2010) The language of histone crosstalk. Cell 142:682–685.  https://doi.org/10.1016/j.cell.2010.08.011CrossRefPubMedPubMedCentralGoogle Scholar
  67. Levanon EY, Eisenberg E, Yelin R et al (2004) Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat Biotechnol 22:1001–1005.  https://doi.org/10.1038/nbt996CrossRefPubMedGoogle Scholar
  68. Licht K, Jantsch MF (2016) Rapid and dynamic transcriptome regulation by RNA editing and RNA modifications. J Cell Biol 213:15–22.  https://doi.org/10.1083/jcb.201511041CrossRefPubMedPubMedCentralGoogle Scholar
  69. Liu J, Yue Y, Han D et al (2014) A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol 10:93–95.  https://doi.org/10.1038/nchembio.1432CrossRefPubMedGoogle Scholar
  70. Liu N, Dai Q, Zheng G et al (2015) N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518:560–564.  https://doi.org/10.1038/nature14234CrossRefPubMedPubMedCentralGoogle Scholar
  71. Machnicka MA, Milanowska K, Osman Oglou O et al (2013) MODOMICS: a database of RNA modification pathways–2013 update. Nucleic Acids Res 41:D262–D267.  https://doi.org/10.1093/nar/gks1007CrossRefPubMedGoogle Scholar
  72. Majid S, Dar AA, Saini S et al (2013) miRNA-34b inhibits prostate cancer through demethylation, active chromatin modifications, and AKT pathways. Clin Cancer Res 19:73–84.  https://doi.org/10.1158/1078-0432.CCR-12-2952CrossRefPubMedGoogle Scholar
  73. Meglicki M, Teperek-Tkacz M, Borsuk E (2012) Appearance and heterochromatin localization of HP1α in early mouse embryos depends on cytoplasmic clock and H3S10 phosphorylation. Cell Cycle Georget Tex 11:2189–2205.  https://doi.org/10.4161/cc.20705CrossRefGoogle Scholar
  74. Mellén M, Ayata P, Dewell S et al (2012) MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 151:1417–1430.  https://doi.org/10.1016/j.cell.2012.11.022CrossRefPubMedPubMedCentralGoogle Scholar
  75. Mercer TR, Mattick JS (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 20:300–307.  https://doi.org/10.1038/nsmb.2480CrossRefPubMedGoogle Scholar
  76. Meyer KD, Jaffrey SR (2014) The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol 15:313–326.  https://doi.org/10.1038/nrm3785CrossRefPubMedPubMedCentralGoogle Scholar
  77. Meyer KD, Saletore Y, Zumbo P et al (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635–1646.  https://doi.org/10.1016/j.cell.2012.05.003CrossRefPubMedPubMedCentralGoogle Scholar
  78. Meyer KD, Patil DP, Zhou J et al (2015) 5′ UTR m(6)A promotes cap-independent translation. Cell 163:999–1010.  https://doi.org/10.1016/j.cell.2015.10.012CrossRefPubMedPubMedCentralGoogle Scholar
  79. Mikkelsen TS, Ku M, Jaffe DB et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553–560.  https://doi.org/10.1038/nature06008CrossRefPubMedPubMedCentralGoogle Scholar
  80. Minarovits J, Banati F, Szenthe K, Niller HH (2016) Epigenetic regulation. In: Minarovits J, Niller HH (eds) Patho-epigenetics of infectious disease. Springer, Cham, pp 1–25CrossRefGoogle Scholar
  81. Murnion ME, Adams RR, Callister DM et al (2001) Chromatin-associated protein phosphatase 1 regulates aurora-B and histone H3 phosphorylation. J Biol Chem 276:26656–26665.  https://doi.org/10.1074/jbc.M102288200CrossRefPubMedGoogle Scholar
  82. Neri F, Incarnato D, Krepelova A et al (2013) Genome-wide analysis identifies a functional association of Tet1 and Polycomb repressive complex 2 in mouse embryonic stem cells. Genome Biol 14:R91.  https://doi.org/10.1186/gb-2013-14-8-r91CrossRefPubMedPubMedCentralGoogle Scholar
  83. Nguyen AT, Zhang Y (2011) The diverse functions of Dot1 and H3K79 methylation. Genes Dev 25:1345–1358.  https://doi.org/10.1101/gad.2057811CrossRefPubMedPubMedCentralGoogle Scholar
  84. Pan W, Zhu S, Yuan M et al (2010) MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol 184:6773–6781.  https://doi.org/10.4049/jimmunol.0904060CrossRefPubMedGoogle Scholar
  85. Pandi G, Nakka VP, Dharap A et al (2013) MicroRNA miR-29c down-regulation leading to de-repression of its target DNA methyltransferase 3a promotes ischemic brain damage. PLoS One 8:e58039.  https://doi.org/10.1371/journal.pone.0058039CrossRefPubMedPubMedCentralGoogle Scholar
  86. Park J-E, Heo I, Tian Y et al (2011) Dicer recognizes the 5′ end of RNA for efficient and accurate processing. Nature 475:201–205.  https://doi.org/10.1038/nature10198CrossRefPubMedPubMedCentralGoogle Scholar
  87. Paul J, Duerksen JD (1975) Chromatin-associated RNA content of heterochromatin and euchromatin. Mol Cell Biochem 9:9–16CrossRefGoogle Scholar
  88. Perry RP, Kelley DE (1974) Existence of methylated messenger RNA in mouse L cells. Cell 1:37–42.  https://doi.org/10.1016/0092-8674(74)90153-6CrossRefGoogle Scholar
  89. Perry RP, Kelley DE, Friderici K, Rottman F (1975) The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5′ terminus. Cell 4:387–394CrossRefGoogle Scholar
  90. Ping X-L, Sun B-F, Wang L et al (2014) Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res 24:177–189.  https://doi.org/10.1038/cr.2014.3CrossRefPubMedPubMedCentralGoogle Scholar
  91. Poulard C, Rambaud J, Hussein N et al (2014) JMJD6 regulates ERα methylation on arginine. PLoS One 9:e87982.  https://doi.org/10.1371/journal.pone.0087982CrossRefPubMedPubMedCentralGoogle Scholar
  92. Quan M, Chen J, Zhang D (2015) Exploring the secrets of long noncoding RNAs. Int J Mol Sci 16:5467–5496.  https://doi.org/10.3390/ijms16035467CrossRefPubMedPubMedCentralGoogle Scholar
  93. Rice GI, Kasher PR, Forte GMA et al (2012) Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat Genet 44:1243–1248.  https://doi.org/10.1038/ng.2414CrossRefPubMedPubMedCentralGoogle Scholar
  94. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166.  https://doi.org/10.1146/annurev-biochem-051410-092902CrossRefPubMedGoogle Scholar
  95. Rinn JL, Kertesz M, Wang JK et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323.  https://doi.org/10.1016/j.cell.2007.05.022CrossRefPubMedPubMedCentralGoogle Scholar
  96. Rodríguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17:330–339.  https://doi.org/10.1038/nm.2305CrossRefPubMedGoogle Scholar
  97. Sabin LR, Delás MJ, Hannon GJ (2013) Dogma derailed: the many influences of RNA on the genome. Mol Cell 49:783–794.  https://doi.org/10.1016/j.molcel.2013.02.010CrossRefPubMedGoogle Scholar
  98. Schermelleh L, Haemmer A, Spada F et al (2007) Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res 35:4301–4312.  https://doi.org/10.1093/nar/gkm432CrossRefPubMedPubMedCentralGoogle Scholar
  99. Schmitz K-M, Mayer C, Postepska A, Grummt I (2010) Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev 24:2264–2269.  https://doi.org/10.1101/gad.590910CrossRefPubMedPubMedCentralGoogle Scholar
  100. Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31:27–36.  https://doi.org/10.1093/carcin/bgp220CrossRefPubMedGoogle Scholar
  101. Shelton SB, Reinsborough C, Xhemalce B (2016) Who watches the watchmen: roles of RNA modifications in the RNA interference pathway. PLoS Genet 12:e1006139.  https://doi.org/10.1371/journal.pgen.1006139CrossRefPubMedPubMedCentralGoogle Scholar
  102. Squires JE, Patel HR, Nousch M et al (2012) Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res 40:5023–5033.  https://doi.org/10.1093/nar/gks144CrossRefPubMedPubMedCentralGoogle Scholar
  103. Struhl K (1998) Histone acetylation and transcriptional regulatory mechanisms. Genes Dev 12:599–606CrossRefGoogle Scholar
  104. Suzuki T, Nagao A, Suzuki T (2011) Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases. Annu Rev Genet 45:299–329.  https://doi.org/10.1146/annurev-genet-110410-132531CrossRefPubMedGoogle Scholar
  105. Suzuki H, Maruyama R, Yamamoto E, Kai M (2012) DNA methylation and microRNA dysregulation in cancer. Mol Oncol 6:567–578.  https://doi.org/10.1016/j.molonc.2012.07.007CrossRefPubMedPubMedCentralGoogle Scholar
  106. Swygert SG, Peterson CL (2014) Chromatin dynamics: interplay between remodeling enzymes and histone modifications. Biochim Biophys Acta 1839:728–736.  https://doi.org/10.1016/j.bbagrm.2014.02.013CrossRefPubMedPubMedCentralGoogle Scholar
  107. Tahiliani M, Koh KP, 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.1170116CrossRefPubMedPubMedCentralGoogle Scholar
  108. Tang Y, Wang J, Lian Y et al (2017) Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer. Mol Cancer 16:42.  https://doi.org/10.1186/s12943-017-0612-0CrossRefPubMedPubMedCentralGoogle Scholar
  109. Torres AG, Batlle E, Ribas de Pouplana L (2014) Role of tRNA modifications in human diseases. Trends Mol Med 20:306–314.  https://doi.org/10.1016/j.molmed.2014.01.008CrossRefPubMedGoogle Scholar
  110. Tsai M-C, Manor O, Wan Y et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693.  https://doi.org/10.1126/science.1192002CrossRefPubMedPubMedCentralGoogle Scholar
  111. Tsuruta T, Kozaki K-I, Uesugi A et al (2011) miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. Cancer Res 71:6450–6462.  https://doi.org/10.1158/0008-5472.CAN-11-0364CrossRefGoogle Scholar
  112. Viré E, Brenner C, Deplus R et al (2006) The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439:871–874.  https://doi.org/10.1038/nature04431CrossRefPubMedGoogle Scholar
  113. Volle C, Dalal Y (2014) Histone variants: the tricksters of the chromatin world. Curr Opin Genet Dev 25(8–14):138.  https://doi.org/10.1016/j.gde.2013.11.006CrossRefGoogle Scholar
  114. Wang X, He C (2014) Dynamic RNA modifications in posttranscriptional regulation. Mol Cell 56:5–12.  https://doi.org/10.1016/j.molcel.2014.09.001CrossRefPubMedGoogle Scholar
  115. Wang KC, Yang YW, Liu B et al (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120–124.  https://doi.org/10.1038/nature09819CrossRefPubMedPubMedCentralGoogle Scholar
  116. Wang X, Lu Z, Gomez A et al (2014a) N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505:117–120.  https://doi.org/10.1038/nature12730CrossRefPubMedGoogle Scholar
  117. Wang Y, Li Y, Toth JI et al (2014b) N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol 16:191–198.  https://doi.org/10.1038/ncb2902CrossRefPubMedPubMedCentralGoogle Scholar
  118. Wang L, Zhao Y, Bao X et al (2015) LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration. Cell Res 25:335–350.  https://doi.org/10.1038/cr.2015.21CrossRefPubMedPubMedCentralGoogle Scholar
  119. Wu H, D’Alessio AC, Ito S et al (2011) Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev 25:679–684.  https://doi.org/10.1101/gad.2036011CrossRefPubMedPubMedCentralGoogle Scholar
  120. Xhemalce B (2013) From histones to RNA: role of methylation in cancer. Brief Funct Genomics 12:244–253.  https://doi.org/10.1093/bfgp/els064CrossRefPubMedGoogle Scholar
  121. Xhemalce B, Robson SC, Kouzarides T (2012) Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell 151:278–288.  https://doi.org/10.1016/j.cell.2012.08.041CrossRefPubMedPubMedCentralGoogle Scholar
  122. Yang X-J, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9:206–218.  https://doi.org/10.1038/nrm2346CrossRefPubMedPubMedCentralGoogle Scholar
  123. Yang L, Lin C, Liu W et al (2011) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147:773–788.  https://doi.org/10.1016/j.cell.2011.08.054CrossRefPubMedPubMedCentralGoogle Scholar
  124. Yi C, Pan T (2011) Cellular dynamics of RNA modification. Acc Chem Res 44:1380–1388.  https://doi.org/10.1021/ar200057mCrossRefPubMedPubMedCentralGoogle Scholar
  125. Yokochi T, Robertson KD (2002) Preferential methylation of unmethylated DNA by mammalian de novo DNA methyltransferase Dnmt3a. J Biol Chem 277:11735–11745.  https://doi.org/10.1074/jbc.M106590200CrossRefPubMedGoogle Scholar
  126. Yuan S, Tang H, Xing J et al (2014) Methylation by NSun2 represses the levels and function of microRNA 125b. Mol Cell Biol 34:3630–3641.  https://doi.org/10.1128/MCB.00243-14CrossRefPubMedPubMedCentralGoogle Scholar
  127. Zhang G, Pradhan S (2014) Mammalian epigenetic mechanisms. IUBMB Life 66:240–256.  https://doi.org/10.1002/iub.1264CrossRefPubMedGoogle Scholar
  128. Zhang B, Liu X-X, He J-R et al (2011) Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer. Carcinogenesis 32:2–9.  https://doi.org/10.1093/carcin/bgq209CrossRefPubMedGoogle Scholar
  129. Zhang K, Sun X, Zhou X et al (2015) Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner. Oncotarget 6:537–546.  https://doi.org/10.18632/oncotarget.2681CrossRefPubMedGoogle Scholar
  130. Zhao S, Wang Y, Liang Y et al (2011) MicroRNA-126 regulates DNA methylation in CD4+ T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1. Arthritis Rheum 63:1376–1386.  https://doi.org/10.1002/art.30196CrossRefPubMedGoogle Scholar
  131. Zhao Y, Sun H, Wang H (2016) Long noncoding RNAs in DNA methylation: new players stepping into the old game. Cell Biosci 6:45.  https://doi.org/10.1186/s13578-016-0109-3CrossRefPubMedPubMedCentralGoogle Scholar
  132. Zheng G, Dahl JA, Niu Y et al (2013) ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 49:18–29.  https://doi.org/10.1016/j.molcel.2012.10.015CrossRefPubMedGoogle Scholar
  133. Zhou J, Wan J, Gao X et al (2015) Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature 526:591–594.  https://doi.org/10.1038/nature15377CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Mansi Arora
    • 1
  • Deepak Kaul
    • 1
  1. 1.Department of Experimental Medicine and BiotechnologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia

Personalised recommendations