New Hope: The Emerging Role of 5-Hydroxymethylcytosine in Mental Health and Disease

References

• Bird A . DNA methylation patterns and epigenetic memory . Genes Dev.16 ( 1 ), 6 – 21 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Sharma RP , GavinDP , GraysonDR . CpG methylation in neurons: message, memory, or mask?Neuropsychopharmacol.35 ( 10 ), 2009 – 2020 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Han JA , AnJ , KoM . Functions of TET proteins in hematopoietic transformation . Mol. Cells38 ( 11 ), 925 – 935 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Suzuki MM , BirdA . DNA methylation landscapes: provocative insights from epigenomics . Nat. Rev. Genet.9 ( 6 ), 465 – 476 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Robertson KD . DNA methylation and human disease . Nat. Rev. Genet.6 ( 8 ), 597 – 610 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Abdolmaleky HM , ChengKH , FaraoneSVet al. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder . Hum. Mol. Genet.15 ( 21 ), 3132 – 3145 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Poulter MO , DuL , WeaverICet al. GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes . Biol. Psychiatry64 ( 8 ), 645 – 652 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Kuratomi G , IwamotoK , BundoMet al. Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins . Mol. Psychiatry13 ( 4 ), 429 – 441 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Kappeler L , MeaneyMJ . Epigenetics and parental effects . Bioessays32 ( 9 ), 818 – 827 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Weaver IC , CervoniN , ChampagneFAet al. Epigenetic programming by maternal behavior . Nat. Neurosci.7 ( 8 ), 847 – 854 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Wu H , ZhangY . Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation . Genes Dev.25 ( 23 ), 2436 – 2452 ( 2011 ).
   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
• 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
• Sun W , ZangL , ShuQ , LiX . From development to diseases: the role of 5hmC in brain . Genomics104 ( 5 ), 347 – 351 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Wang J , TangJ , LaiM , ZhangH . 5-hydroxymethylcytosine and disease . Mutat. Res. Rev. Mutat. Res.762167 – 175 ( 2014 ).
   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
• 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
• Kraus TF , KilincS , SteinmaurerM , StieglitzM , GuibourtV , KretzschmarHA . Profiling of methylation and demethylation pathways during brain development and ageing . J. Neural. Transm. (Vienna)123 ( 3 ), 189 – 203 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Cheng X . Structure and function of DNA methyltransferases . Annu. Rev. Biophys. Biomol. Struct.24 , 293 – 318 ( 1995 ).
   PubMedGoogle Scholar
• Okano M , BellDW , HaberDA , LiE . DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development . Cell99 , 247 – 257 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Sharp AJ , StathakiE , MigliavaccaEet al. DNA methylation profiles of human active and inactive X chromosomes . Genome Res.21 , 1592 – 1600 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Ioshikhes IP , ZhangMQ . Large-scale human promoter mapping using CpG islands . Nat. Genet.26 ( 1 ), 61 – 63 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Irier HA , JinP . Dynamics of DNA methylation in aging and Alzheimer’s disease . CellBiol.31 ( Suppl. 1 ), S42 – S48 ( 2012 ).
   Google Scholar
• Frommer M , McDonaldLE , MillarDSet al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands . Proc. Natl Acad. Sci. USA89 ( 5 ), 1827 – 1831 ( 1992 ).
   PubMed Web of Science ®Google Scholar
• Song CX , SzulwachKE , FuYet al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine . Nat. Biotechnol.29 ( 1 ), 68 – 72 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Branco MR , FiczG , ReikW . Uncovering the role of 5-hydroxymethylcytosine in theepigenome . Nat. Rev. Genet.13 , 7 – 13 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Chopra P , PapaleLA , WhiteATet al. Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice . BMC Genomics15 , 131 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Khare T , PaiS , KonceviciusKet al. 5-hmC in the brain is abundant in synaptic genes and shows differences at the exon–intron boundary . Nat. Struct. Mol. Biol.19 ( 10 ), 1037 – 1043 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Li S , PapaleLA , ZhangQet al. Genome-wide alterations in hippocampal 5-hydroxymethylcytosine links plasticity genes to acute stress . Neurobiol. Dis.86 , 99 – 108 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Gross JA , PacisA , ChenGGet al. Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution . BMC Genomics16 , 672 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Feng J , ShaoN , SzulwachKEet al. Role of Tet1 and 5-hydroxymethylcytosine in cocaine action . Nat. Neurosci.18 ( 4 ), 536 – 544 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Yu M , HonGC , SzulwachKEet al. Tet-assisted bisulfite sequencing of 5-hydroxymethylcytosine . Nat. Protoc.7 ( 12 ), 2159 – 2170 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Phase IMA , QiuR , WuXet al. Dynamics of 5-hydroxymethylcytosine and chromatin marks in mammalian neurogenesis . Cell Rep.3 ( 2 ), 291 – 300 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Tan L , XiongL , XuWet al. Genome-wide comparison of DNA hydroxymethylation in mouse embryonic stem cells and neural progenitor cells by a new comparative hMeDIP-seq method . Nucleic Acids Res.41 ( 7 ), e84 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kang J , LienhardM , PastorWAet al. Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis . Proc. Natl Acad. Sci. USA112 ( 31 ), E4236 – E4245 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Szulwach KE , LiX , LiYet al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging . Nat. Neurosci.14 ( 12 ), 1607 – 1616 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Chen H , DzitoyevaS , ManevH . Effect of aging on 5-hydroxymethylcytosine in the mouse hippocampus . Restor. Neurol. Neurosci.30 ( 3 ), 237 – 245 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Zampieri M , CiccaroneF , CalabreseR , FranceschiC , BurkleA , CaiafaP . Reconfiguration of DNA methylation in aging . Mech. Ageing Dev.151 , 60 – 70 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Chouliaras L , Van Den HoveDL , KenisGet al. Age-related increase in levels of 5-hydroxymethylcytosine in mouse hippocampus is prevented by caloric restriction . Curr. Alzheimer Res.9 ( 5 ), 536 – 544 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Al-Mahdawi S , VirmouniSA , PookMA . The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases . Front. Neurosci.8 , 397 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Chouliaras L , MastroeniD , DelvauxEet al. Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer’s disease patients . Neurobiol. Aging34 ( 9 ), 2091 – 2099 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Condliffe D , WongA , TroakesCet al. Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer’s disease brain . Neurobiol. Aging35 ( 8 ), 1850 – 1854 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Coppieters N , DieriksBV , LillC , FaullRL , CurtisMA , DragunowM . Global changes in DNA methylation and hydroxymethylation in Alzheimer’s disease human brain . Neurobiol. Aging35 ( 6 ), 1334 – 1344 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Bradley-Whitman MA , LovellMA . Epigenetic changes in the progression of Alzheimer’s disease . Mech. Ageing Dev.134 ( 10 ), 486 – 495 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lashley T , GamiP , ValizadehN , LiA , ReveszT , BalazsR . Alterations in global DNA methylation and hydroxymethylation are not detected in Alzheimer’s disease . Neuropathol. Appl. Neurobiol.41 ( 4 ), 497 – 506 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Walker FO . Huntington’s disease . Lancet369 ( 9557 ), 218 – 228 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Lee J , HwangYJ , KimKY , KowallNW , RyuH . Epigenetic mechanisms of neurodegeneration in Huntington’s disease . Neurotherapeutics10 ( 4 ), 664 – 676 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Reik W , MaherER , MorrisonPJ , HardingAE , SimpsonSA . Age at onset in Huntington’s disease and methylation at D4S95 . J. Med. Genet.30 ( 3 ), 185 – 188 ( 1993 ).
   PubMed Web of Science ®Google Scholar
• Wang F , YangY , LinXet al. Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington’s disease . Hum. Mol. Genet.22 ( 18 ), 3641 – 3653 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Villar-Menendez I , BlanchM , TyebjiSet al. Increased 5-methylcytosine and decreased 5-hydroxymethylcytosine levels are associated with reduced striatal A2AR levels in Huntington’s disease . Neuromolecular Med.15 ( 2 ), 295 – 309 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• McKinnon PJ . ATM and ataxia telangiectasia . EMBO Rep.5 ( 8 ), 772 – 776 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Jiang D , ZhangY , HartRP , ChenJ , HerrupK , LiJ . Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency . Brain138 ( Pt 12 ), 3520 – 3536 ( 2015 ).
   PubMedGoogle Scholar
• Hagerman PJ , HagermanRJ . Fragile X-associated tremor/ataxia syndrome . Ann. NY Acad. Sci.1338 , 58 – 70 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Santoro MR , BraySM , WarrenST . Molecular mechanisms of fragile X syndrome: a twenty-year perspective . Annu. Rev. Pathol.7 , 219 – 245 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Yao B , LinL , StreetRCet al. Genome-wide alteration of 5-hydroxymethylcytosine in a mouse model of fragile X-associated tremor/ataxia syndrome . Hum. Mol. Genet.23 ( 4 ), 1095 – 1107 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Irier H , StreetRC , DaveRet al. Environmental enrichment modulates 5-hydroxymethylcytosine dynamics in hippocampus . Genomics104 ( 5 ), 376 – 382 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Li S , PapaleLA , KintnerDBet al. Hippocampal increase of 5-hmC in the glucocorticoid receptor gene following acute stress . Behav. Brain Res.286 , 236 – 240 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Cirelli C , FaragunaU , TononiG . Changes in brain gene expression after long-term sleep deprivation . J. Neurochem.98 ( 5 ), 1632 – 1645 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Li X , WeiW , ZhaoQYet al. Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation . Proc. Natl Acad. Sci. USA111 ( 19 ), 7120 – 7125 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Rudenko A , DawlatyMM , SeoJet al. Tet1 is critical for neuronal activity-regulated gene expression and memory extinction . Neuron79 ( 6 ), 1109 – 1122 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Roth TL , SweattJD . Epigenetic marking of the BDNF gene by early-life adverse experiences . Horm. Behav.59 ( 3 ), 315 – 320 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Labonte B , SudermanM , MaussionGet al. Genome-wide epigenetic regulation by early-life trauma . Arch. Gen. Psychiatry69 ( 7 ), 722 – 731 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• McGowan PO , SasakiA , D’AlessioACet al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse . Nat. Neurosci.12 ( 3 ), 342 – 348 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Oberlander TF , WeinbergJ , PapsdorfM , GrunauR , MisriS , DevlinAM . Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses . Epigenetics3 ( 2 ), 97 – 106 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Massart R , SudermanM , ProvencalNet al. Hydroxymethylation and DNA methylation profiles in the prefrontal cortex of the non-human primate rhesus macaque and the impact of maternal deprivation on hydroxymethylation . Neuroscience268139 – 148 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Koenig JI , ElmerGI , ShepardPDet al. Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia . Behav. Brain Res.156 ( 2 ), 251 – 261 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Guidotti A , DongE , TuetingP , GraysonDR . Modeling the molecular epigenetic profile of psychosis in prenatally stressed mice . Prog. Mol. Biol. Transl. Sci.128 , 89 – 101 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Matrisciano F , TuetingP , DalalIet al. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice . Neuropharmacol.68 , 184 – 194 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Brown AS . The environment and susceptibility to schizophrenia . Prog. Neurobiol.93 ( 1 ), 23 – 58 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Dong E , GavinDP , ChenY , DavisJ . Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients . Transl. Psychiatry2 , e159 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Tseng PT , LinPY , LeeYet al. Age-associated decrease in global DNA methylation in patients with major depression . Neuropsychiatr. Dis. Treat.10 , 2105 – 2114 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Gaugler T , KleiL , SandersSJet al. Most genetic risk for autism resides with common variation . Nat. Genet.46 ( 8 ), 881 – 885 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Bulik-Sullivan B , FinucaneHK , AnttilaVet al. An atlas of genetic correlations across human diseases and traits . Nat. Genet.47 ( 11 ), 1236 – 1241 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Gardener H , SpiegelmanD , BukaSL . Prenatal risk factors for autism: comprehensive meta-analysis . Br. J. Psychiatry195 ( 1 ), 7 – 14 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Rogers EJ . Has enhanced folate status during pregnancy altered natural selection and possibly Autism prevalence? A closer look at a possible link . Med. Hypotheses71 ( 3 ), 406 – 410 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Wang T , PanQ , LinLet al. Genome-wide DNA hydroxymethylation changes are associated with neurodevelopmental genes in the developing human cerebellum . Hum. Mol. Genet.21 ( 26 ), 5500 – 5510 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Penagarikano O , LazaroMT , LuXHet al. Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism . Sci. Transl. Med.7 ( 271 ), 271ra – 278 ( 2015 ).
   Web of Science ®Google Scholar
• Penagarikano O , AbrahamsBS , HermanEIet al. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits . Cell147 ( 1 ), 235 – 246 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Papale LA , ZhangQ , LiS , ChenK , KelesS , AlischRS . Genome-wide disruption of 5-hydroxymethylcytosine in a mouse model of autism . Hum. Mol. Genet.24 ( 24 ), 7121 – 7131 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Van Den Hove DL , JakobSB , SchrautKGet al. Differential effects of prenatal stress in 5-Htt deficient mice: towards molecular mechanisms of gene × environment interactions . PLoS ONE6 ( 8 ), e22715 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Feng J , WilkinsonM , LiuXet al. Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens . Genome Biol.15 ( 4 ), R65 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Rodgers AB , MorganCP , BronsonSL , RevelloS , BaleTL . Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation . J. Neurosci.33 ( 21 ), 9003 – 9012 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Szyf M . Epigenetics, a key for unlocking complex CNS disorders? Therapeutic implications . Eur. Neuropsychopharmacol.25 ( 5 ), 682 – 702 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Nolen-Hoeksema S . Sex differences in unipolar depression: evidence and theory . Psychol. Bull.101 ( 2 ), 259 – 282 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Wooten GF , CurrieLJ , BovbjergVE , LeeJK , PatrieJ . Are men at greater risk for Parkinson’s disease than women?J. Neurol. Neurosurg. Psychiatry75 ( 4 ), 637 – 639 ( 2004 ).
   PubMed Web of Science ®Google Scholar