The Role of DNA Methylation in Zebrafish Models of CNS Diseases

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Abstract

DNA methylation plays an important role in the regulation of gene expression. Disturbances in this process in the brain cause various neurological diseases, including autism, schizophrenia and mood disorders. Zebrafish (Danio rerio) are a promising model organism in biomedicine. Given high genetic and physiological homology with humans, studying genome methylation deficits in zebrafish can help to clarify the molecular processes underlying etiology and pathogenesis of various neurological diseases, as well as to develop novel therapies. Here, we discuss the mechanisms of DNA methylation in the brain and the diseases associated with its dysregulation in humans, as well as their genetic and pharmacological models in zebrafish. We also evaluate the limitations of zebrafish models and possible directions for further research in this field. Mounting evidence summarized here supports zebrafish as an effective model for elucidating the molecular mechanisms of brain pathologies associated with impaired DNA methylation.

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About the authors

L. V. Yushko

Almazov National Medical Research Center, Ministry of Healthcare; St. Petersburg State University

Email: avkalueff@gmail.com

World-class scientific center “Center for Personalized Medicine”, Institute of Experimental Medicine, Institute of Translational Biomedicine

Russian Federation, St. Petersburg; St. Petersburg

A. D. Shevlyakov

Almazov National Medical Research Center, Ministry of Healthcare; Sirius University of Science and Technology

Email: avkalueff@gmail.com

World-class scientific center “Center for Personalized Medicine”, Neurobiology Program, Scientific Center for Genetics and Life Sciences

Russian Federation, St. Petersburg; Federal Territory Sirius

M. A. Romazeva

Sirius University of Science and Technology

Email: avkalueff@gmail.com

Neurobiology Program, Scientific Center for Genetics and Life Sciences

Russian Federation, Federal Territory Sirius

K. V. Apukhtin

Sirius University of Science and Technology

Email: avkalueff@gmail.com

Neurobiology Program, Scientific Center for Genetics and Life Sciences

Russian Federation, Federal Territory Sirius

A. D. Volgin

Sirius University of Science and Technology

Email: avkalueff@gmail.com

Neurobiology Program, Scientific Center for Genetics and Life Sciences

Russian Federation, Federal Territory Sirius

D. A. Abramov

Sirius University of Science and Technology

Email: avkalueff@gmail.com

Neurobiology Program, Scientific Center for Genetics and Life Sciences

Russian Federation, Federal Territory Sirius

M. M. Kotova

Sirius University of Science and Technology

Email: avkalueff@gmail.com

Neurobiology Program, Scientific Center for Genetics and Life Sciences

Russian Federation, Federal Territory Sirius

A. V. Kalueff

Almazov National Medical Research Center, Ministry of Healthcare; St. Petersburg State University; Sirius University of Science and Technology; Research Institute of Neuroscience and Medicine

Author for correspondence.
Email: avkalueff@gmail.com

World-class scientific center “Center for Personalized Medicine”, Institute of Experimental Medicine, Institute of Translational Biomedicine, Neurobiology Program, Scientific Center for Genetics and Life Sciences

Russian Federation, St. Petersburg; St. Petersburg; Federal Territory Sirius; Novosibirsk

References

  1. Mattei AL, Bailly N, Meissner A (2022) DNA methylation: a historical perspective. Trends Genet 38: 676–707. https://doi.org/10.1016/j.tig.2022.03.010
  2. Bashirzade AA, Zabegalov KN, Volgin AD, Belova AS, Demin KA, de Abreu MS, Babchenko VY, Bashirzade KA, Yenkoyan KB, Tikhonova MA, Amstislavskaya TG, Kalueff AV (2022) Modeling neurodegenerative disorders in zebrafish. Neurosci Biobehav Rev 138: 104679. https://doi.org/10.1016/j.neubiorev.2022.104679
  3. Dang M, Henderson RE, Garraway LA, Zon LI (2016) Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies. Dis Mod Mech 9: 811–820. https://doi.org/10.1242/dmm.024166
  4. Wang J, Cao H (2021) Zebrafish and Medaka: important animal models for human neurodegenerative diseases. Intl J Mol Sci 22: 10766. https://doi.org/10.3390/ijms221910766
  5. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L, McLaren S, Sealy I, Caccamo M, Churcher C, Scott C, Barrett JC, Koch R, Rauch GJ, White S, Chow W, Kilian B, Quintais LT, Guerra-Assunção JA, Zhou Y, Gu Y, Yen J, Vogel JH, Eyre T, Redmond S, Banerjee R, Chi J, Fu B, Langley E, Maguire SF, Laird GK, Lloyd D, Kenyon E, Donaldson S, Sehra H, Almeida-King J, Loveland J, Trevanion S, Jones M, Quail M, Willey D, Hunt A, Burton J, Sims S, McLay K, Plumb B, Davis J, Clee C, Oliver K, Clark R, Riddle C, Elliot D, Threadgold G, Harden G, Ware D, Begum S, Mortimore B, Kerry G, Heath P, Phillimore B, Tracey A, Corby N, Dunn M, Johnson C, Wood J, Clark S, Pelan S, Griffiths G, Smith M, Glithero R, Howden P, Barker N, Lloyd C, Stevens C, Harley J, Holt K, Panagiotidis G, Lovell J, Beasley H, Henderson C, Gordon D, Auger K, Wright D, Collins J, Raisen C, Dyer L, Leung K, Robertson L, Ambridge K, Leongamornlert D, McGuire S, Gilderthorp R, Griffiths C, Manthravadi D, Nichol S, Barker G, Whitehead S, Kay M, Brown J, Murnane C, Gray E, Humphries M, Sycamore N, Barker D, Saunders D, Wallis J, Babbage A, Hammond S, Mashreghi-Mohammadi M, Barr L, Martin S, Wray P, Ellington A, Matthews N, Ellwood M, Woodmansey R, Clark G, Cooper J, Tromans A, Grafham D, Skuce C, Pandian R, Andrews R, Harrison E, Kimberley A, Garnett J, Fosker N, Hall R, Garner P, Kelly D, Bird C, Palmer S, Gehring I, Berger A, Dooley CM, Ersan-Ürün Z, Eser C, Geiger H, Geisler M, Karotki L, Kirn A, Konantz J, Konantz M, Oberländer M, Rudolph-Geiger S, Teucke M, Lanz C, Raddatz G, Osoegawa K, Zhu B, Rapp A, Widaa S, Langford C, Yang F, Schuster SC, Carter NP, Harrow J, Ning Z, Herrero J, Searle SM, Enright A, Geisler R, Plasterk RH, Lee C, Westerfield M, de Jong PJ, Zon LI, Postlethwait JH, Nüsslein-Volhard C, Hubbard TJ, Roest Crollius H, Rogers J, Stemple DL (2013) The zebrafish reference genome sequence and its relationship to the human genome. Nature 496: 498–503. https://doi.org/10.1038/nature12111
  6. Shin JT, Priest JR, Ovcharenko I (2005) Human-zebrafish non-coding conserved elements act in vivo to regulate transcription. Nucl Acid Res 33: 5437–5445. https://doi.org/10.1093/nar/gki853
  7. Vilella AJ, Severin J, Ureta-Vidal A, Heng L, Durbin R, Birney E (2009) EnsemblCompara GeneTrees: Complete, duplication-aware phylogenetic trees in vertebrates. Genome Res 19: 327–335. https://doi.org/10.1101/gr.073585.107
  8. Kim DS, Huh JW, Kim YH, Park SJ, Kim HS, Chang KT (2010) Bioinformatic analysis of TE-spliced new exons within human, mouse and zebrafish genomes. Genomics 96: 266–271. https://doi.org/10.1016/j.ygeno.2010.08.004
  9. Berma J, Payne E, Hall C (2012) The zebrafish as a tool to study hematopoiesis, human blood diseases, and immune function. Adv Hematol 2012: 425345. https://doi.org/10.1155/2012/425345
  10. Taylor JS, Braasch I, Frickey T, Meyer A, Van de Peer Y (2003) Genome duplication, a trait shared by 22000 species of ray-finned fish. Genome Res 13: 382–390. https://doi.org/10.1101/gr.640303
  11. Mihaljevic I, Popovic M, Zaja R, Smital T (2016) Phylogenetic, syntenic, and tissue expression analysis of slc22 genes in zebrafish (Danio rerio). BMC Genom 17: 626. https://doi.org/10.1186/s12864–016–2981-y
  12. McCammon JM, Sive H (2015) Challenges in understanding psychiatric disorders and developing therapeutics: a role for zebrafish. Dis Mod Mech 8: 647–656. https://doi.org/10.1242/dmm.019620
  13. Varshney GK, Sood R, Burgess SM (2015) Understanding and editing the zebrafish genome. Adv Gen 92: 1–52. https://doi.org/10.1016/bs.adgen.2015.09.002
  14. Yushko LV, Kalueff AV, Kotova MM (2023) Experimental models of mitochondrial dysfunction disorders in the pathogenesis of CNS diseases on zebrafish. J Evol Biochem Physiol 59: 2114–2128.
  15. Zhang L, Lu Q, Chang C (2020) Epigenetics in health and disease. Adv Exper Med Biol 1253: 3–55. https://doi.org/10.1007/978–981–15–3449–2_1
  16. Gayon J (2016) From Mendel to epigenetics: history of genetics. Comptes Rendus Biol 339: 225–230. https://doi.org/10.1016/j.crvi.2016.05.009
  17. Edwards JR, Yarychkivska O, Boulard M, Bestor TH (2017) DNA methylation and DNA methyltransferases. Epigenet Chromatin 10: 23. https://doi.org/10.1186/s13072–017–0130–8
  18. Hamidi T, Singh AK, Chen T (2015) Genetic alterations of DNA methylation machinery in human diseases. Epigenomics 7: 247–265. https://doi.org/10.2217/epi.14.80
  19. Ren Y (2022) Regulatory mechanism and biological function of UHRF1-DNMT1-mediated DNA methylation. Funct Integr Genom 22: 1113–1126. https://doi.org/10.1007/s10142–022–00918–9
  20. Qin L, Qiao C, Sheen V, Wang Y, Lu J (2021) DNMT3L promotes neural differentiation by enhancing STAT1 and STAT3 phosphorylation independent of DNA methylation. Prog Neurobiol 201: 102028. https://doi.org/10.1016/j.pneurobio.2021.102028
  21. Gujar H, Weisenberger DJ, Liang G (2019) The roles of human DNA methyltransferases and their isoforms in shaping the epigenome. Genes 10: 172. https://doi.org/10.3390/genes10020172
  22. Younesian S, Yousefi AM, Momeny M, Ghaffari SH, Bashash D (2022) The DNA methylation in neurological diseases. Cells 11: 3439. https://doi.org/10.3390/cells11213439
  23. Pensold D, Reichard J, Van Loo KMJ, Ciganok N, Hahn A, Bayer C, Liebmann L, Groß J, Tittelmeier J, Lingner T, Salinas-Riester G, Symmank J, Halfmann C, González-Bermúdez L, Urbach A, Gehrmann J, Costa I, Pieler T, Hübner CA, Vatter H, Kampa B, Becker AG, Zimmer-Bensch G (2020) DNA methylation-mediated modulation of endocytosis as potential mechanism for synaptic function regulation in murine inhibitory cortical interneurons. Cereb Cortex 30: 3921–3937. https://doi.org/10.1093/cercor/bhaa009
  24. Sergeeva A, Davydova K, Perenkov A, Vedunova M (2023) Mechanisms of human DNA methylation, alteration of methylation patterns in physiological processes and oncology. Gene 875: 147487. https://doi.org/10.1016/j.gene.2023.147487
  25. Hanaki S, Habara M, Shimada M (2021) UV-induced activation of ATR is mediated by UHRF2. Gen Cells 26: 447–454. https://doi.org/10.1111/gtc.12851
  26. Xavier MJ, Roman SD, Aitken RJ, Nixon B (2019) Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health. Hum Repr Update 25: 518–540. https://doi.org/10.1093/humupd/dmz017
  27. Inaba Y, Iwamoto S, Nakayama K (2022) Genome-wide DNA methylation status of Mongolians exhibits signs of cellular stress response related to their nomadic lifestyle. J Phys Anthropol 41: 30. https://doi.org/10.1186/s40101–022–00305–0
  28. Lunnon K, Harvey J, Smith A, Weymouth L, Smith R, Castanho I, Hubbard L, Creese B, Bresner K, Williams N, Pishva E (2023) Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: A DNA co-methylation network analysis. Res Square rs.3.rs-3185734. https://doi.org/10.21203/rs.3.rs-3185734/v1
  29. Abomoelak B, Prather R, Pragya SU, Pragya SC, Mehta ND, Uddin P, Veeramachaneni P, Mehta N, Young A, Kapoor S, Mehta D (2023) Cognitive skills and DNA methylation are correlating in healthy and novice college students practicing Preksha Dhyāna meditation. Brain Sci 13: 1214. https://doi.org/10.3390/brainsci13081214
  30. Cavalieri V, Spinelli G (2017) Environmental epigenetics in zebrafish. Epigen. Chromat 10: 46. https://doi.org/10.1186/s13072–017–0154–0
  31. Lakstygal AM, de Abreu MS, Kalueff AV (2018) Zebrafish models of epigenetic regulation of CNS functions. Brain Res Bull 142: 344–351. https://doi.org/10.1016/j.brainresbull.2018.08.022
  32. Swartz ME, Wells MB, Griffin M, McCarthy N, Lovely CB, McGurk P, Rozacky J, Eberhart JK (2014) A screen of zebrafish mutants identifies ethanol-sensitive genetic loci. Alcohol Clin Exp Res 38: 694–703. https://doi.org/10.1111/acer.12286
  33. Knecht AL, Truong L, Marvel SW, Reif DM, Garcia A, Lu C, Simonich MT, Teeguarden JG, Tanguay RL (2017) Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish. Toxicol Appl Pharmacol 329: 148–157. https://doi.org/10.1016/j.taap.2017.05.033
  34. Jacob J, Ribes V, Moore S, Constable SC, Sasai N, Gerety SS, Martin DJ, Sergeant CP, Wilkinson DG, Briscoe J (2014) Valproic acid silencing of ascl1b/Ascl1 results in the failure of serotonergic differentiation in a zebrafish model of fetal valproate syndrome. Dis Mod Mech 7: 107–117. https://doi.org/10.1242/dmm.013219
  35. Wang L, Jiang W, Lin Q, Zhang Y, Zhao C (2016) DNA methylation regulates gabrb2 mRNA expression: developmental variations and disruptions in l-methionine-induced zebrafish with schizophrenia-like symptoms. Genes Brain Behav 15: 702–710. https://doi.org/10.1111/gbb.12315
  36. Razali K, Othman N, Mohd Nasir MH, Doolaanea AA, Kumar J, Ibrahim WN, Mohamed Ibrahim N, Mohamed WMY (2021) The promise of the zebrafish model for Parkinson's disease: today's science and tomorrow's treatment. Front Genet 12: 655550. https://doi.org/10.3389/fgene.2021.655550
  37. Zheng YC, Ma J, Wang Z, Li J, Jiang B, Zhou W, Shi X, Wang X, Zhao W, Liu HM (2015) A Systematic Review of Histone Lysine-Specific Demethylase 1 and Its Inhibitors. Medicin Res Rev 35: 1032–1071. https://doi.org/10.1002/med.21350
  38. Meshcheryakova A, Pietschmann P, Zimmermann P, Rogozin IB, Mechtcheriakova D (2021) AID and APOBECs as multifaceted intrinsic virus-restricting factors: emerging concepts in the light of COVID-19. Front Immunol 12: 690416. https://doi.org/10.3389/fimmu.2021.690416
  39. Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR (2008) DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 135: 1201–1212. https://doi.org/10.1016/j.cell.2008.11.042
  40. Popp C, Dean W, Feng S, Cokus SJ, Andrews S, Pellegrini M, Jacobsen SE, Reik W (2010) Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463: 1101–1105. https://doi.org/10.1038/nature08829
  41. Sandweiss AJ, Brandt VL, Zoghbi HY (2020) Advances in understanding of Rett syndrome and MECP2 duplication syndrome: prospects for future therapies. Lancet Neurol 19: 689–698. https://doi.org/10.1016/S1474–4422(20)30217–9
  42. Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S, Hojo K, Yamanishi H, Karpf AR, Wallace DC, Simon M, Lander C, Boardman LA, Cunningham JM, Smith GE, Litchy WJ, Boes B, Atkinson EJ, Middha S, B Dyck PJ, Parisi JE, Mer G, Smith DI, Dyck PJ (2011) Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet 43: 595–600. https://doi.org/10.1038/ng.830
  43. Protic DD, Aishworiya R, Salcedo-Arellano MJ, Tang SJ, Milisavljevic J, Mitrovic F, Hagerman RJ, Budimirovic DB (2022) Fragile X Syndrome: from molecular aspect to clinical treatment. Intl J Mol Sci 23: 1935. https://doi.org/10.3390/ijms23041935
  44. Yamada M, Okuno H, Okamoto N, Suzuki H, Miya F, Takenouchi T, Kosaki K (2023) Diagnosis of Prader-Willi syndrome and Angelman syndrome by targeted nanopore long-read sequencing. Eur J Med Genet 66: 104690. https://doi.org/10.1016/j.ejmg.2022.104690
  45. Sheikhpour M, Maleki M, Ebrahimi Vargoorani M, Amiri V (2021) A review of epigenetic changes in asthma: methylation and acetylation. Clin Epigenet 13: 65. https://doi.org/10.1186/s13148–021–01049-x
  46. Browne CJ, Godino A, Salery M, Nestler EJ (2020) Epigenetic mechanisms of opioid addiction. Biol Psychiatry 87: 22–33. https://doi.org/10.1016/j.biopsych.2019.06.027
  47. Vrettou M, Yan L, Nilsson KW, Wallén-Mackenzie Å, Nylander I, Comasco E (2021) DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early-life stress and adult ethanol exposure-an explorative study. Sci Reports 11: 15322. https://doi.org/10.1038/s41598–021–94739–8
  48. Demidenko O, Barardo D, Budovskii V, Finnemore R, Palmer FR, Kennedy BK, Budovskaya YV (2021) Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8-year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging 13: 24485–24499. https://doi.org/10.18632/aging.203736
  49. McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12: 342–348. https://doi.org/10.1038/nn.2270
  50. Xiu J, Li J, Liu Z, Wei H, Zhu C, Han R, Liu Z, Zhu W, Shen Y, Xu Q (2022) Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice. Proc Natl Acad Sci U S A 119: e2201967119. https://doi.org/10.1073/pnas.2201967119
  51. Nguyen M, Stewart AM, Kalueff AV (2014) Aquatic blues: modeling depression and antidepressant action in zebrafish. Prog Neuropsychopharmacol Biol Psychiatry 55: 26–39. https://doi.org/10.1016/j.pnpbp.2014.03.003
  52. Babin PJ, Goizet C, Raldúa D (2014) Zebrafish models of human motor neuron diseases: advantages and limitations. Prog Neurobiol 118: 36–58. https://doi.org/10.1016/j.pneurobio.2014.03.001
  53. Liu Y, Siejka-Zielińska P, Velikova G, Bi Y, Yuan F, Tomkova M, Bai C, Chen L, Schuster-Böckler B, Song CX (2019) Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution. Nat Biotechnol 37: 424–429. https://doi.org/10.1038/s41587–019–0041–2
  54. Wu Y, Vasung L, Calixto C, Gholipour A, Karimi D (2023) Characterizing normal perinatal development of the human brain structural connectivity. ArXiv, arXiv: 2308.11836v1.
  55. Zhang C, Hoshida Y, Sadler KC (2016) Comparative epigenomic profiling of the DNA methylome in mouse and zebrafish uncovers high interspecies divergence. Front Genet 7: 110. https://doi.org/10.3389/fgene.2016.00110
  56. Lee HJ, Lowdon RF, Maricque B, Zhang B, Stevens M, Li D, Johnson SL, Wang T (2015) Developmental enhancers revealed by extensive DNA methylome maps of zebrafish early embryos. Nat Commun 6: 6315. https://doi.org/10.1038/ncomms7315
  57. Kapusta A, Kronenberg Z, Lynch VJ, Zhuo X, Ramsay L, Bourque G, Yandell M, Feschotte C (2013) Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLoS Genet 9: e1003470. https://doi.org/10.1371/journal.pgen.1003470
  58. Xin N, Wang DT, Zhang L, Zhou Y, Cheng Y (2022) Early developmental stage glucocorticoid exposure causes DNA methylation and behavioral defects in adult zebrafish. Comp Biochem Physiol Pt C: Toxicol Pharmacol 256: 109301. https://doi.org/10.1016/j.cbpc.2022.109301
  59. Guo W, Han J, Wu S, Shi X, Wang Q, Zhou B (2019) Bis (2-ethylhexyl)-2, 3, 4, 5-tetrabromophthalate affects lipid metabolism in zebrafish larvae via DNA methylation modification. Env Sci Тechnol 54: 355–363. https://doi.org/10.1021/acs.est.9b05796
  60. Benvenutti R, Gallas-Lopes M, Marcon M, Reschke CR, Herrmann AP, Piato A (2022) Glutamate NMDA receptor antagonists with relevance to schizophrenia: a review of zebrafish behavioral studies. Curr Neuropharmacol 20: 494. https://doi.org/10.2174/1570159X19666210215121428
  61. Zhai G, Jia J, Bereketoglu C, Yin Z, Pradhan A (2022) Sex-specific differences in zebrafish brains. Biol Sex Differ 13: 31. https://doi.org/10.1186/s13293–022–00442–2
  62. McEwen BS, Milner TA (2017) Understanding the broad influence of sex hormones and sex differences in the brain. J Neurosci Res 95: 24–39. https://doi.org/10.1002/jnr.23809
  63. Young LJ, Pfaff DW (2014) Sex differences in neurological and psychiatric disorders. Front Neuroendocrinol 35: 253–254. https://doi.org/10.1016/j.yfrne.2014.05.005
  64. Chatterjee A, Lagisz M, Rodger EJ, Zhen L, Stockwell PA, Duncan EJ, Horsfield JA, Jeyakani J, Mathavan S, Ozaki Y, Nakagawa S (2016) Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive' hypothesis. Gene 590: 307–316. https://doi.org/10.1016/j.gene.2016.05.042
  65. Serikuly N, Alpyshov ET, Wang D, Wang J, Yang L, Hu G, Yan D, Demin KA, Kolesnikova TO, Galstyan D, Amstislavskaya TG, Babashev AM, Mor MS, Efimova EV, Gainetdinov RR, Strekalova T, de Abreu MS, Song C, Kalueff AV (2021) Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia. Prog Neuropsychopharmacol Biol Psychiatry 104: 109977. https://doi.org/10.1016/j.pnpbp.2020.109977
  66. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302: 890–893. https://doi.org/10.1126/science.1090842
  67. Xie J, Xie L, Wei H, Li XJ, Lin L (2023) Dynamic regulation of DNA methylation and brain functions. Biology 12: 152. https://doi.org/10.3390/biology12020152
  68. Wu H, Coskun V, Tao J, Xie W, Ge W, Yoshikawa K, Li E, Zhang Y, Sun YE (2010) Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science 329: 444–448. https://doi.org/10.1126/science.1190485
  69. Cruceanu C, Kutsarova E, Chen ES, Checknita DR, Nagy C, Lopez JP, Turecki G (2016) DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression. BMC Psychiatry 16: 1–5. https://doi.org/10.1186/s12888–016–0989–0
  70. Zhu Y, Gomez JA, Laufer BI, Mordaunt CE, Mouat JS, Soto DC, LaSalle JM (2022) Placental methylome reveals a 22q13. 33 brain regulatory gene locus associated with autism. Genome Biol 23: 1–32. https://doi.org/10.1186/s13059–022–02613–1
  71. Kohli RM, Zhang Y (2013) TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502: 472–479. https://doi.org/10.1038/nature12750
  72. Kamstra JH, Løken M, Aleström P, Legler J (2015) Dynamics of DNA hydroxymethylation in zebrafish. Zebrafish 12: 230–237. https://doi.org/10.1089/zeb.2014.1033
  73. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR (2013) Global epigenomic reconfiguration during mammalian brain development. Science 341: 1237905. https://doi.org/10.1126/science.1237905
  74. Jang HS, Shin WJ, Lee JE, Do JT (2017) CpG and non-CpG methylation in epigenetic gene regulation and brain function. Genes 8: 148. https://doi.org/10.3390/genes8060148
  75. Chen L, Chen K, Lavery LA, Baker SA, Shaw CA, Li W, Zoghbi HY (2015) MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. Proc Natl Acad Sciences U S A 112: 5509–5514. https://doi.org/10.1073/pnas.1505909112
  76. Strömqvist M, Tooke N, Brunström B (2010) DNA methylation levels in the 5' flanking region of the vitellogenin I gene in liver and brain of adult zebrafish (Danio rerio) – sex and tissue differences and effects of 17alpha-ethinylestradiol exposure. Aquat Toxicol 98: 275–281. https://doi.org/10.1016/j.aquatox.2010.02.023
  77. Khor YM, Soga T, Parhar IS (2016) Early-life stress changes expression of GnRH and kisspeptin genes and DNA methylation of GnRH3 promoter in the adult zebrafish brain. Gen Comp Endocrinol 227: 84–93. https://doi.org/10.1016/j.ygcen.2015.12.004
  78. Li R, Yang L, Han J, Zou Y, Wang Y, Feng C, Zhou B (2021) Early-life exposure to tris (1,3-dichloro-2-propyl) phosphate caused multigenerational neurodevelopmental toxicity in zebrafish via altering maternal thyroid hormones transfer and epigenetic modifications. Environ Pollut 285: 117471. https://doi.org/10.1016/j.envpol.2021.117471
  79. Xu J, Zhang W, Zhong S, Xie X, Che H, Si W, Tuo X, Xu D, Zhao S (2023) Microcystin-leucine-arginine affects brain gene expression programs and behaviors of offspring through paternal epigenetic information. Sci Total Environ 857: 159032. https://doi.org/10.1016/j.scitotenv.2022.159032

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2. Fig. 1. The main mechanisms of gene transcription control by DNA methylation. The top two examples show the inhibition of transcription by preventing the interaction of transcription factors with the promoter and enhancer regions of the gene, respectively. When the promoter is methylated, an activating protein (AP) is involved, which prevents transcription factors from binding to the promoter sequence. The example below reflects the interaction of methyl-CpG-binding protein (MBP) with a region enriched with methylated CpG sites. After binding MBP to the DNA sequence, histone deacetylases (HDA) are involved, which deacetylate histones, leading to chromatin condensation at this site and closure of promoters for binding transcription factors, which, in turn, turns off gene expression.

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3. Fig. 2. The role of DNA methylation and demethylation in the regulation of nervous tissue functions. Native cytosine undergoes methylation due to the action of three main methyltransferases: Dnmt3a, Dnmt3b, Dnmt3L. At the same time, the continuous methylation process is supported by Dnmt1. The passive demethylation process is carried out by external factors. The process of active demethylation is performed by TET-methylcytosine dioxygenase (TET) and thymine DNA glycosylase (TDG), (see also Table 2).

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4. Fig. 3. The effect of environmental factors on changes in gene expression during DNA methylation in the main cell types of the zebradanio brain. TET – Tet-methylcytosine dioxygenases, enzymes of genome demethylation; DNMTs – DNA methyltransferases, enzymes of genome methylation (see also Figs. 1 and 2).

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5. Fig. 4. The effect of methylation of marker gene promoters on the development of zebradanio CNS phenotypes. Hypermethylation of the promoter of the glucocorticoid receptor nr3c1 gene alters its expression and, as a result, the normal functioning of the hypothalamic-pituitary-adrenal axis, enhancing anxiety-like behavior in fish [58]. The lack of methylation of the promoter of the peroxisome proliferator-activated gamma receptor (pparg) gene, a key transcription factor that controls the expression of many downstream genes involved in lipid transport, biogenesis and lipolysis, leads to an increase in pparg expression. In turn, this causes a rapid accumulation of ATP and an abnormal increase in the locomotor activity of zebrafish fry [59]. The glutamate ionotropic receptor and its subunit 1 (grin1) play an important role in the mechanism of pathogenesis of memory impairment, the promoter of which gene is hypermethylated under the influence of nicotine in fish (and in rats), which leads to suppression of expression

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