254
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Dysregulation of Schizophrenia-Associated Genes and Genome-Wide Hypomethylation in Neurons Overexpressing DNMT1

, , , , ORCID Icon & ORCID Icon
Pages 1539-1555 | Received 22 Apr 2021, Accepted 20 Sep 2021, Published online: 14 Oct 2021

References

  • Murray CJ , LopezAD. A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. In: Global Burden of Disease and Injury Series. Harvard Unversity Press, ISBN 0-9655466-0-8, 1–43 (1996).
  • Cardno AG , GottesmanII. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am. J. Med. Genet.97(1), 12–17 (2000).
  • Zhang Y , ReinbergD. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev.15(18), 2343–2360 (2001).
  • Bestor TH , EdwardsJR , BoulardM. Notes on the role of dynamic DNA methylation in mammalian development. Proc. Natl Acad. Sci. USA112(22), 6796–6799 (2015).
  • Seto E , YoshidaM. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb. Perspect. Biol.6(4), a018713 (2014).
  • Maltby VE , MartinBJE , Brind’AmourJet al. Histone H3K4 demethylation is negatively regulated by histone H3 acetylation in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA109(45), 18505–18510 (2012).
  • Schomacher L . Mammalian DNA demethylation: multiple faces and upstream regulation. Epigenetics8(7), 679–684 (2013).
  • Zhang L , LuQ , ChangC. Epigenetics in health and disease. Adv. Exp. Med. Biol.1253, 3–55 (2020).
  • Torabi Moghadam B , EtemadikhahM , RajkowskaGet al. Analyzing DNA methylation patterns in subjects diagnosed with schizophrenia using machine learning methods. J. Psychiatr. Res.114, 41–47 (2019).
  • Akbarian S , RuehlMG , BlivenEet al. Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia. Arch. Gen. Psychiatry62(8), 829–840 (2005).
  • Perkins DO , JeffriesCD , JarskogLFet al. microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol.8(2), R27 (2007).
  • Bahari-Javan S , VarbanovH , HalderRet al. HDAC1 links early life stress to schizophrenialike phenotypes. Proc. Natl Acad. Sci. USA114(23), E4686–E4694 (2017).
  • Schroeder FA , GilbertTM , FengNet al. Expression of HDAC2 but not HDAC1 transcript is reduced in dorsolateral prefrontal cortex of patients with schizophrenia. ACS Chem. Neurosci.8(3), 662–668 (2017).
  • Sharma RP , GraysonDR , GavinDP. Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: analysis of the National Brain Databank microarray collection. Schizophr. Res.98(1–3), 111–117 (2008).
  • Zhubi A , VeldicM , PuriNVet al. An upregulation of DNA-methyltransferase 1 and 3a expressed in telencephalic GABAergic neurons of schizophrenia patients is also detected in peripheral blood lymphocytes. Schizophr. Res.111(1–3), 115–122 (2009).
  • Veldic M , CarunchoHJ , LiuWSet al. DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc. Natl Acad. Sci. USA101(1), 348–353 (2004).
  • Veldic M , GuidottiA , MalokuE , DavisJM , CostaE. In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc. Natl Acad. Sci. USA102(6), 2152–2157 (2005).
  • Kundakovic M , ChenY , CostaE , GraysonDR. DNA methyltransferase inhibitors coordinately induce expression of the human reelin and glutamic acid decarboxylase 67 genes. Mol. Pharmacol.71(3), 644–653 (2007).
  • Biniszkiewicz D , GribnauJ , RamsahoyeBet al. DNMT1 overexpression causes genomic hypermethylation, loss of imprinting, and embryonic lethality. Mol. Cell. Biol.22(7), 2124–2135 (2002).
  • D’Aiuto L , DiMaio R , MohanKNet al. Mouse ES cells overexpressing DNMT1 produce abnormal neurons with upregulated NMDA/NR1 subunit. Differentiation82(1), 9–17 (2011).
  • Sen GL , ReuterJA , WebsterDE , ZhuL , KhavariPA. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature463(7280), 563–567 (2010).
  • Mohan KN . Stem cell models to investigate the role of DNA methylation machinery in development of neuropsychiatric disorders. Stem Cells Int.2016, 4379425 (2016).
  • Saxena S , MarojuPA , ChoudhuryS , AnneA , MohanKN. Analysis of transcript levels of a few schizophrenia candidate genes in neurons from a transgenic mouse embryonic stem cell model overexpressing DNMT1. Gene757, 144934 (2020).
  • Fromer M , RoussosP , SiebertsSKet al. Gene expression elucidates functional impact of polygenic risk for schizophrenia. Nat. Neurosci.19(11), 1442–1453 (2016).
  • Gandal MJ , ZhangP , HadjimichaelEet al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science362(6420), 1–32 (2019).
  • Jaffe AE , StraubRE , ShinJHet al. Developmental and genetic regulation of the human cortex transcriptome illuminate schizophrenia pathogenesis. Nat. Neurosci.21(8), 1117–1125 (2019).
  • Saxena S , ChoudhuryS , MohanKN. Reproducible differentiation and characterization of neurons from mouse embryonic stem cells. MethodsX7, 101073 (2020).
  • Saxena S , ChoudhuryS , MohanKN. Genome-wide methylation data from R1 (wild-type) and the transgenic DNMT1Tet/Tet mouse embryonic stem cells overexpressing DNA methyltransferase 1 (DNMT1). Data Br.32, 106242 (2020).
  • Feng H , ConneelyKN , WuH. A Bayesian hierarchical model to detect differentially methylated loci from single nucleotide resolution sequencing data. Nucleic Acids Res.42(8), 1–11 (2014).
  • Park Y , WuH. Differential methylation analysis for BS-seq data under general experimental design. Bioinformatics32(10), 1446–1453 (2016).
  • Livak KJ , SchmittgenTD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods25(4), 402–408 (2001).
  • Szklarczyk D , GableAL , LyonDet al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res.47(D1), D607–D613 (2019).
  • Xiong Z , LairdPW. COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res.25(12), 2532–2534 (1997).
  • D’Haene B , VandesompeleJ , HellemansJ. Accurate and objective copy number profiling using real-time quantitative PCR. Methods50(4), 262–270 (2010).
  • Xu J , HaoZ , GouXet al. Imaging of reactive oxygen species burst from mitochondria using laser scanning confocal microscopy. Microsc. Res. Tech.76(6), 612–617 (2013).
  • Borowczyk E , MohanKN , D’AiutoL , CirioMC , ChailletJR. Identification of a region of the DNMT1 methyltransferase that regulates the maintenance of genomic imprints. Proc. Natl Acad. Sci. USA106(49), 20806–20811 (2009).
  • Peng Y , XuY , CuiD. Wnt signaling pathway in schizophrenia. CNS & Neurological Disorders – Drug Targets13(5), 755–764 (2014).
  • Funk AJ , McCullumsmithRE , HaroutunianV , Meador-WoodruffJH. Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia. Neuropsychopharmacology37(4), 896–905 (2012).
  • Berretta S . Extracellular matrix abnormalities in schizophrenia. Neuropharmacology62(3), 1584–1597 (2012).
  • Wang Z , LiP , WuT , ZhuS , DengL , CuiG. Axon guidance pathway genes are associated with schizophrenia risk. Exp. Ther. Med.16(6), 4519–4526 (2018).
  • Ashton A , JagannathA. Disrupted sleep and circadian rhythms in schizophrenia and their interaction with dopamine signaling. Front. Neurosci.14, 1–14 (2020).
  • Kalkman HO . Altered growth factor signaling pathways as the basis of aberrant stem cell maturation in schizophrenia. Pharmacol. Ther.121(1), 115–122 (2009).
  • Jarskog LF , GlantzLA , GilmoreJH , LiebermanJA. Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog. Neuro-Psychopharmacology Biol. Psychiatry29(5), 846–858 (2005).
  • Robicsek O , KarryR , PetitIet al. Abnormal neuronal differentiation and mitochondrial dysfunction in hair follicle-derived induced pluripotent stem cells of schizophrenia patients. Mol. Psychiatry18(10), 1067–1076 (2013).
  • Tucker KL , BeardC , DausmanJet al. Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes. Genes Dev.10(8), 1008–1020 (1996).
  • Yang YJ , LuoT , ZhaoYet al. Altered insulin-like growth factor-2 signaling is associated with psychopathology and cognitive deficits in patients with schizophrenia. PLoS ONE15(3), 1–13 (2020).
  • Gardiner E , BeveridgeNJ , WuJQet al. Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells. Mol. Psychiatry17(8), 827–840 (2012).
  • Karis K , EsklaKL , KaareMet al. Altered expression profile of igLON family of neural cell adhesion molecules in the dorsolateral prefrontal cortex of schizophrenic patients. Front. Mol. Neurosci.11, 1–12 (2018).
  • Crespi B , ReadS , SalminenI , HurdP. A genetic locus for paranoia. Biol. Lett.14(1), 1–5 (2018).
  • Konopaske GT , SubburajuS , CoyleJT , BenesFM. Altered prefrontal cortical MARCKS and PPP1R9A mRNA expression in schizophrenia and bipolar disorder. Schizophr. Res.164(1–3), 100–108 (2015).
  • Baylin SB . DNA methylation and gene silencing in cancer. Nat. Clin. Pract. Oncol.2, 4–11 (2005).
  • Newell-Price J , ClarkAJL , KingP. DNA methylation and silencing of gene expression. Trends Endocrinol. Metab.11(4), 142–148 (2000).
  • Clements EG , MohammadHP , LeademBRet al. DNMT1 modulates gene expression without its catalytic activity partially through its interactions with histone-modifying enzymes. Nucleic Acids Res.40(10), 4334–4346 (2012).
  • Espada J . Non-catalytic functions of DNMT1. Epigenetics7(2), 115–118 (2012).
  • Doyle GA , CristRC , KaratasETet al. Analysis of LINE-1 elements in DNA from postmortem brains of individuals with schizophrenia. Neuropsychopharmacology42(13), 2602–2611 (2017).
  • Guffanti G , GaudiS , KlengelTet al. LINE1 insertions as a genomic risk factor for schizophrenia: preliminary evidence from an affected family. Am. J. Med. Genet. Part B Neuropsychiatr. Genet.171(4), 534–545 (2016).
  • Li S , YangQ , HouYet al. Hypomethylation of LINE-1 elements in schizophrenia and bipolar disorder. J. Psychiatr. Res.107, 68–72 (2018).
  • Misiak B , SzmidaE , KarpińskiP , LoskaO , SąsiadekMM , FrydeckaD. Lower LINE-1 methylation in first-episode schizophrenia patients with the history of childhood trauma. Epigenomics7(8), 1275–1285 (2015).
  • Terry DM , DevineSE. Aberrantly high levels of somatic LINE-1 expression and retro transposition in human neurological disorders. Front. Genet.10, 1–14 (2020).
  • Kalayasiri R , KraijakK , MutiranguraA , MaesM. Paranoid schizophrenia and methamphetamine-induced paranoia are both characterized by a similar LINE-1 partial methylation profile, which is more pronounced in paranoid schizophrenia. Schizophr. Res.208, 221–227 (2019).
  • Shpyleva S , MelnykS , PavlivO , PogribnyI , JillJames S. Overexpression of LINE-1 retrotransposons in autism brain. Mol. Neurobiol.55(2), 1740–1749 (2018).
  • Dong E , GavinDP , ChenY , DavisJ. Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients. Transl. Psychiatry2, 1–7 (2012).
  • Kwon W , KimHS , JeongJet al. Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice. FASEB J.32(1), 390–403 (2018).
  • Dong E , ChenY , GavinDP , GraysonDR , GuidottiA. Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. Epigenetics5(8), 730–735 (2010).
  • Smith RC , LindenmayerJP , DavisJMet al. Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder. Schizophr. Res.110(1–3), 149–155 (2009).
  • Matrisciano F , DongE , NicolettiF , GuidottiA. Epigenetic alterations in prenatal stress mice as an endophenotype model for schizophrenia: role of metabotropic glutamate 2/3 receptors. Front. Mol. Neurosci.11, 1–8 (2018).
  • Dong E , RuzickaWB , GraysonDR , GuidottiA. DNA-methyltransferase1 (DNMT1) binding to CpG rich GABAergic and BDNF promoters is increased in the brain of schizophrenia and bipolar disorder patients. Schizophr. Res.167(1–3), 35–41 (2015).
  • Miller JL , GrantPA. The role of DNA methylation and histone modifications in transcriptional regulation in humans. Subcell Biochem.61, 289–317 (2013).
  • Barbot W , DupressoirA , LazarV , HeidmannT. Epigenetic regulation of an IAP retrotransposon in the aging mouse: progressive demethylation and de-silencing of the element by its repetitive induction. Nucleic Acids Res.30(11), 2365–2373 (2002).
  • Lane N , DeanW , ErhardtSet al. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis35(2), 88–93 (2003).
  • Belancio VP , HedgesDJ , DeiningerP. LINE-1 RNA splicing and influences on mammalian gene expression. Nucleic Acids Res.34(5), 1512–1521 (2006).
  • Murata Y , IkegameT , KoikeSet al. Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia. Prog. Neuro-Psychopharmacology Biol. Psychiatry99, 109855 (2020).
  • Shimabukuro M , SasakiT , ImamuraAet al. Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: a potential link between epigenetics and schizophrenia. J. Psychiatr. Res.41(12), 1042–1046 (2007).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.