The Elusive Role of 5′-Hydroxymethylcytosine

References

• Wyatt GR , CohenSS . The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine . Biochem. J.55 ( 5 ), 774 – 782 ( 1953 ).
   PubMed Web of Science ®Google Scholar
• Flaks JG , LichtensteinJ , CohenSS . Virus-induced acquisition of metabolic function. II. Studies on the origin of the deoxycytidylate hydroxymethylase of bacteriophage-infected E. coli . J. Biol. Chem.234 ( 6 ), 1507 – 1511 ( 1959 ).
   PubMed Web of Science ®Google Scholar
• Penn NW , SuwalskiR , O’RileyC , BojanowskiK , YuraR . The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid . Biochem. J.126 ( 4 ), 781 – 790 ( 1972 ).
   PubMed Web of Science ®Google Scholar
• Kothari RM , ShankarV . 5-Methylcytosine content in the vertebrate deoxyribonucleic acids: species specificity . J. Mol. Evol.7 ( 4 ), 325 – 329 ( 1976 ).
   PubMed Web of Science ®Google Scholar
• Kriaucionis S , HeintzN . The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain . Science324 ( 5929 ), 929 – 930 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Bachman M , Uribe-LewisS , YangX , WilliamsM , MurrellA , BalasubramanianS . 5-Hydroxymethylcytosine is a predominantly stable DNA modification . Nat. Chem.6 ( 12 ), 1049 – 1055 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Shi Y , LanF , MatsonCet al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 . Cell119 ( 7 ), 941 – 953 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Tsukada Y , FangJ , Erdjument-BromageHet al. Histone demethylation by a family of JmjC domain-containing proteins . Nature439 ( 7078 ), 811 – 816 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Falnes PO , JohansenRF , SeebergE . AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli . Nature419 ( 6903 ), 178 – 182 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Kurowski MA , BhagwatAS , PapajG , BujnickiJM . Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB . BMC Genomics4 ( 1 ), 48 ( 2003 ).
   PubMedGoogle Scholar
• Taylor SM , JonesPA . Mechanism of action of eukaryotic DNA methyltransferase. Use of 5- azacytosine-containing DNA . J. Mol. Biol.162 ( 3 ), 679 – 692 ( 1982 ).
   PubMed Web of Science ®Google Scholar
• Cheng X , BlumenthalRM . Mammalian DNA methyltransferases: a structural perspective . Structure16 ( 3 ), 341 – 350 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Razin A , RiggsAD . DNA methylation and gene function . Science210 ( 4470 ), 604 – 610 ( 1980 ).
   PubMed Web of Science ®Google Scholar
• Oswald J , EngemannS , LaneNet al. Active demethylation of the paternal genome in the mouse zygote . Curr. Biol.10 ( 8 ), 475 – 478 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Hajkova P , ErhardtS , LaneNet al. Epigenetic reprogramming in mouse primordial germ cells . Mech. Dev.117 ( 1–2 ), 15 – 23 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Hajkova P , JeffriesSJ , LeeC , MillerN , JacksonSP , SuraniMA . Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway . Science329 ( 5987 ), 78 – 82 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Hamm S , JustG , LacosteN , MoitessierN , SzyfM , MamerO . On the mechanism of demethylation of 5-methylcytosine in DNA . Bioorg. Med. Chem. Lett.18 , 1046 – 1049 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Ito S , D’AlessioAC , TaranovaOV , HongK , SowersLC , ZhangY . Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification . Nature466 ( 7310 ), 1129 – 1133 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Song CX , DiaoJ , BrungerAT , QuakeSR . Simultaneous single-molecule epigenetic imaging of DNA methylation and hydroxymethylation . Proc. Natl Acad. Sci. USA113 ( 16 ), 4338 – 4343 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Tahiliani M , KohKP , ShenYet al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 . Science324 ( 5929 ), 930 – 935 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Williams K , ChristensenJ , PedersenMTet al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity . Nature473 ( 7347 ), 343 – 348 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Kaas GA , ZhongC , EasonDEet al. TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation . Neuron79 ( 6 ), 1086 – 1093 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Koh KP , YabuuchiA , RaoSet al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells . Cell Stem Cell8 ( 2 ), 200 – 213 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Shen L , WuH , DiepDet al. Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics . Cell153 ( 3 ), 692 – 706 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Ichiyama K , ChenT , WangXet al. The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells . Immunity42 ( 4 ), 613 – 626 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Ito S , ShenL , DaiQet al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine . Science333 ( 6047 ), 1300 – 1303 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• He YF , LiBZ , LiZet al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA . Science333 ( 6047 ), 1303 – 1307 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Hashimoto H , HongS , BhagwatAS , ZhangX , ChengX . Excision of 5-hydroxymethyluracil and 5-carboxylcytosine by the thymine DNA glycosylase domain: its structural basis and implications for active DNA demethylation . Nucleic Acids Res.40 ( 20 ), 10203 – 10214 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Iqbal K , JinSG , PfeiferGP , SzaboPE . Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine . Proc. Natl Acad. Sci. USA108 ( 9 ), 3642 – 3647 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Inoue A , ShenL , DaiQ , HeC , ZhangY . Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation development . Cell Res.21 ( 12 ), 1670 – 1676 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Arand J , WossidloM , LepikhovK , PeatJR , ReikW , WalterJ . Selective impairment of methylation maintenance is the major cause of DNA methylation reprogramming in the early embryo . Epigenetics Chromatin8 ( 1 ), 1 ( 2015 ).
   PubMedGoogle Scholar
• Petrussa L , Van De VeldeH , De RyckeM . Similar kinetics for 5-methylcytosine and 5-hydroxymethylcytosine during human preimplantation development in vitro . Mol. Reprod. Dev.83 ( 7 ), 594 – 605 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Ohno R , NakayamaM , NaruseCet al. A replication-dependent passive mechanism modulates DNA demethylation in mouse primordial germ cells . Development140 ( 14 ), 2892 – 2903 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kagiwada S , KurimotoK , HirotaT , YamajiM , SaitouM . Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice . EMBO J.32 ( 3 ), 340 – 353 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Tang WW , DietmannS , IrieNet al. A unique gene regulatory network resets the human germline epigenome for development . Cell161 ( 6 ), 1453 – 1467 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Von Meyenn F , IurlaroM , HabibiEet al. Impairment of DNA methylation maintenance is the main cause of global demethylation in naive embryonic stem cells . Mol. Cell62 ( 6 ), 848 – 861 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Guo F , LiX , LiangDet al. Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote . Cell Stem Cell15 ( 4 ), 447 – 458 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Maiti A , DrohatAC . Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites . J. Biol. Chem.286 ( 41 ), 35334 – 35338 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Zhang P , HuangB , XuX , SessaWC . Ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG), components of the demethylation pathway, are direct targets of miRNA-29a . Biochem. Biophys. Res. Commun.437 ( 3 ), 368 – 373 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kohli RM , ZhangY . TET enzymes, TDG and the dynamics of DNA demethylation . Nature502 ( 7472 ), 472 – 479 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Dalton SR , BellacosaA . DNA demethylation by TDG . Epigenomics4 ( 4 ), 459 – 467 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Weber AR , KrawczykC , RobertsonABet al. Biochemical reconstitution of TET1-TDG-BER-dependent active DNA demethylation reveals a highly coordinated mechanism . Nat. Commun.7 , 10806 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Peat JR , DeanW , ClarkSJet al. Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation . Cell Rep.9 ( 6 ), 1990 – 2000 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Shen L , InoueA , HeJ , LiuY , LuF , ZhangY . Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes . Cell Stem Cell15 ( 4 ), 459 – 470 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Gruenbaum Y , CedarH , RazinA . Substrate and sequence specificity of a eukaryotic DNA methylase . Nature295 ( 5850 ), 620 – 622 ( 1982 ).
   PubMed Web of Science ®Google Scholar
• Valinluck V , SowersLC . Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1 . Cancer Res.67 ( 3 ), 946 – 950 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Otani J , KimuraH , SharifJet al. Cell cycle-dependent turnover of 5-hydroxymethyl cytosine in mouse embryonic stem cells . PLoS ONE8 ( 12 ), e82961 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Guo JU , SuY , ZhongC , MingGL , SongH . Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain . Cell145 ( 3 ), 423 – 434 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Chen H , KazemierHG , De GrooteML , RuitersMH , XuGL , RotsMG . Induced DNA demethylation by targeting ten-eleven translocation 2 to the human ICAM-1 promoter . Nucleic Acids Res.42 ( 3 ), 1563 – 1574 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Jin C , LuY , JelinekJet al. TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells . Nucleic Acids Res.42 ( 11 ), 6956 – 6971 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Delhommeau F , DupontS , Della ValleVet al. Mutation in TET2 in myeloid cancers . N. Engl. J. Med.360 ( 22 ), 2289 – 2301 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Abdel-Wahab O , MullallyA , HedvatCet al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies . Blood114 ( 1 ), 144 – 147 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Ko M , HuangY , JankowskaAMet al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 . Nature468 ( 7325 ), 839 – 843 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Rasmussen KD , JiaG , JohansenJVet al. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis . Genes Dev.29 ( 9 ), 910 – 922 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Figueroa ME , Abdel-WahabO , LuCet al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation . Cancer Cell18 ( 6 ), 553 – 567 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Feng J , ChangH , LiE , FanG . Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system . J. Neurosci. Res.79 ( 6 ), 734 – 746 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Hu L , LuJ , ChengJet al. Structural insight into substrate preference for TET-mediated oxidation . Nature527 ( 7576 ), 118 – 122 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Ramchandani S , BhattacharyaSK , CervoniN , SzyfM . DNA methylation is a reversible biological signal . Proc. Natl Acad. Sci. USA96 ( 11 ), 6107 – 6112 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Mitra S , IzumiT , BoldoghI , BhakatKK , HillJW , HazraTK . Choreography of oxidative damage repair in mammalian genomes . Free Radic. Biol. Med.33 ( 1 ), 15 – 28 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Bachman M , Uribe-LewisS , YangXet al. 5-Formylcytosine can be a stable DNA modification in mammals . Nat. Chem. Biol.11 ( 8 ), 555 – 557 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Blaschke K , EbataKT , KarimiMMet al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells . Nature500 ( 7461 ), 222 – 226 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Ruiz MA , RiversA , IbanezVet al. Hydroxymethylcytosine and demethylation of the gamma-globin gene promoter during erythroid differentiation . Epigenetics10 ( 5 ), 397 – 407 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Yin R , MaoSQ , ZhaoBet al. Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals . J. Am. Chem. Soc.135 ( 28 ), 10396 – 10403 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lister R , MukamelEA , NeryJRet al. Global epigenomic reconfiguration during mammalian brain development . Science341 ( 6146 ), 1237905 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Serandour AA , AvnerS , OgerFet al. Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers . Nucleic Acids Res.40 ( 17 ), 8255 – 8265 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Guo JU , MaDK , MoHet al. Neuronal activity modifies the DNA methylation landscape in the adult brain . Nat. Neurosci.14 ( 10 ), 1345 – 1351 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Bogdanovic O , SmitsAH , De La Calle MustienesEet al. Active DNA demethylation at enhancers during the vertebrate phylotypic period . Nat. Genet.48 ( 4 ), 417 – 426 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Putiri EL , TiedemannRL , ThompsonJJet al. Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells . Genome Biol.15 ( 6 ), R81 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Yamazaki J , JelinekJ , LuYet al. TET2 mutations affect non-CpG island DNA methylation at enhancers and transcription factor-binding sites in chronic myelomonocytic leukemia . Cancer Res.75 ( 14 ), 2833 – 2843 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Yang YA , ZhaoJC , FongKWet al. FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function . Nucleic Acids Res. doi:10.1093/nar/gkw498 ( 2016 ) ( Epub ahead of print ).
   Web of Science ®Google Scholar
• Wen L , LiX , YanLet al. Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain . Genome Biol.15 ( 3 ), R49 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Ivanov M , KalsM , LauschkeVet al. Single base resolution analysis of 5-hydroxymethylcytosine in 188 human genes: implications for hepatic gene expression . Nucleic Acids Res. doi:10.1093/nar/gkw316 ( 2016 ) ( Epub ahead of print ).
   Web of Science ®Google Scholar
• Yu M , HonGC , SzulwachKEet al. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome . Cell149 ( 6 ), 1368 – 1380 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Nestor CE , OttavianoR , ReinhardtDet al. Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems . Genome Biol.16 , 11 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Uribe-Lewis S , StarkR , CarrollTet al. 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer . Genome Biol.16 ( 1 ), 69 ( 2015 ).
   PubMedGoogle Scholar
• Spruijt CG , GnerlichF , SmitsAHet al. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives . Cell152 ( 5 ), 1146 – 1159 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Yang R , QuC , ZhouYet al. Hydrogen sulfide promotes Tet1- and Tet2-mediated Foxp3 demethylation to drive regulatory T cell differentiation and maintain immune homeostasis . Immunity43 ( 2 ), 251 – 263 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Wang L , LiuY , HanRet al. Mbd2 promotes foxp3 demethylation and T-regulatory-cell function . Mol. Cell. Biol.33 ( 20 ), 4106 – 4115 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Roszczyk E , GoodgalS . Methylase activities from Haemophilus influenzae that protect Haemophilus parainfluenzae transforming deoxyribonucleic acid from inactivation by Haemophilus influenzae endonuclease R . J. Bacteriol.123 ( 1 ), 287 – 293 ( 1975 ).
   PubMed Web of Science ®Google Scholar
• Comb M , GoodmanHM . CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2 . Nucleic Acids Res.18 ( 13 ), 3975 – 3982 ( 1990 ).
   PubMed Web of Science ®Google Scholar
• Meehan RR , LewisJD , McKayS , KleinerEL , BirdAP . Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs . Cell58 ( 3 ), 499 – 507 ( 1989 ).
   PubMed Web of Science ®Google Scholar
• Yildirim O , LiR , HungJHet al. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells . Cell147 ( 7 ), 1498 – 1510 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Baubec T , IvanekR , LienertF , SchubelerD . Methylation-dependent and -independent genomic targeting principles of the MBD protein family . Cell153 ( 2 ), 480 – 492 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Mellen M , AyataP , DewellS , KriaucionisS , HeintzN . MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system . Cell151 ( 7 ), 1417 – 1430 ( 2012 ).
   PubMed Web of Science ®Google Scholar