TET1 displays catalytic and non-catalytic functions in the adult mouse cortex

References

• Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet. 2017;18(9):517–24. doi: 10.1038/nrg.2017.33
   PubMed Web of Science ®Google Scholar
• Kohli RM, Zhang Y. REVIEW TET enzymes, TDG and the dynamics of DNA demethylation. Nature. 2013;502(7472):472–479. doi: 10.1038/nature12750
   PubMed Web of Science ®Google Scholar
• Hu L, Li Z, Cheng J, et al. Crystal structure of TET2-DNA complex: insight into TET-Mediated 5mC oxidation. Cell. 2013;155(7):1545–1555. doi: 10.1016/j.cell.2013.11.020
   PubMed Web of Science ®Google Scholar
• Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–935. doi: 10.1126/science.1170116
   PubMed Web of Science ®Google Scholar
• Lorsback RB, Moore J, Mathew S, et al. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;23) [3]. Leukemia. 2003;17(3):637–641. doi: 10.1038/sj.leu.2402834
   PubMed Web of Science ®Google Scholar
• Ono R, Taki T, Taketani T, et al. LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res. 2002;62(62):4075–4080.
   PubMedGoogle Scholar
• Münzel M, Globisch D, Brückl T, et al. Quantification of the sixth DNA base hydroxymethylcytosine in the brain. Angew Chem - Int Ed. 2010;49(31):5375–5377. doi: 10.1002/anie.201002033
   PubMed Web of Science ®Google Scholar
• Mellén M, Ayata P, Heintz N. 5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes. Proc Natl Acad Sci USA. 2017;114(37):E7812–E7821. doi: 10.1073/pnas.1708044114
   PubMed Web of Science ®Google Scholar
• Szulwach KE, Li X, Li Y, et al. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLOS Genet. 2011;7(6):e1002154. doi: 10.1371/journal.pgen.1002154
   PubMed Web of Science ®Google Scholar
• Kaas GA, Zhong C, Eason D, et al. TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation. Neuron. 2013;79(6):1086–1093. doi: 10.1016/j.neuron.2013.08.032
   PubMed Web of Science ®Google Scholar
• Kumar D, Aggarwal M, Kaas GA, et al. Tet1 oxidase regulates neuronal gene transcription, active DNA hydroxymethylation, object location memory, and threat recognition memory. Neuroepigenetics. 2015;4:12–27. doi: 10.1016/j.nepig.2015.10.002
   PubMedGoogle Scholar
• Rudenko A, Dawlaty M, Seo J, et al. Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron. 2013;79(6):1109–1122. doi: 10.1016/j.neuron.2013.08.003
   PubMed Web of Science ®Google Scholar
• Sun Z, Xu X, He J, et al. EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity. Nat Commun. 2019;10(1):1–12. doi: 10.1038/s41467-019-11905-3
   PubMedGoogle Scholar
• Chrysanthou S, Tang Q, Lee J, et al. The DNA dioxygenase Tet1 regulates H3K27 modification and embryonic stem cell biology independent of its catalytic activity. Nucleic Acids Res. 2022;50(6):3169–3189. doi: 10.1093/nar/gkac089
   PubMed Web of Science ®Google Scholar
• Williams K, Christensen J, Pedersen MT, et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature. 2011;473(7347):343–348. doi: 10.1038/nature10066
   PubMed Web of Science ®Google Scholar
• Tsai Y, Chen H-F, Chen S-Y, et al. TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator. Genome Biol. 2014;15(12):1–13. doi: 10.1186/s13059-014-0513-0
   Web of Science ®Google Scholar
• Ito K, Lee J, Chrysanthou S, et al. Non-catalytic roles of Tet2 are essential to regulate hematopoietic stem and progenitor cell homeostasis. Cell Rep. 2019;28(10):2480–2490.e4. doi: 10.1016/j.celrep.2019.07.094
   PubMed Web of Science ®Google Scholar
• Ko M, Huang Y, Jankowska AM, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 2010;468(7325):839–843. doi: 10.1038/nature09586
   PubMed Web of Science ®Google Scholar
• Caldwell BA, Liu MY, Prasasya RD, et al. Functionally distinct roles for TET-oxidized 5-methylcytosine bases in somatic reprogramming to pluripotency. Mol Cell. 2021;81(4):859–869.e8. doi: 10.1016/j.molcel.2020.11.045
   PubMed Web of Science ®Google Scholar
• Prasasya RD, Caldwell BA, Liu Z, et al. Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions. Dev Cell. 2024;59(8):1010–1027.e8. doi: 10.1016/j.devcel.2024.02.012
   PubMedGoogle Scholar
• Dawlaty M, Breiling A, Le T, et al. Combined deficiency of Tet1 and Tet2 Causes Epigenetic Abnormalities but is compatible with postnatal development. Dev Cell. 2013;24(3):310–323. doi: 10.1016/j.devcel.2012.12.015
   PubMed Web of Science ®Google Scholar
• Zhou W, Hinoue T, Barnes B, et al. DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse. Cell Genomics. 2022;2(7):100144. doi: 10.1016/j.xgen.2022.100144
   PubMedGoogle Scholar
• Schutsky EK, DeNizio JE, Hu P, et al. Nondestructive, base-resolution sequencing of 5-hydroxymethylcytosine using a DNA deaminase. Nat Biotechnol. 2018;36(11):1083–1090. doi: 10.1038/nbt.4204
   Web of Science ®Google Scholar
• Song C, Szulwach KE, Fu Y, et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol. 2011;29(1):68–72. doi: 10.1038/nbt.1732
   PubMed Web of Science ®Google Scholar
• Dawlaty MM, Ganz K, Powell B, et al. Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell. 2011;9(2):166–175. doi: 10.1016/j.stem.2011.07.010
   PubMed Web of Science ®Google Scholar
• Juan AM, Foong YH, Thorvaldsen JL, et al. Tissue-specific Grb10/Ddc insulator drives allelic architecture for cardiac development. Mol Cell. 2022;82(19):3613–3631.e7. doi: 10.1016/j.molcel.2022.08.021
   PubMed Web of Science ®Google Scholar
• Fabyanic EB, Hu P, Qiu Q, et al. Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects. Nat Biotechnol. 2023;42(6):960–974. doi: 10.1038/s41587-023-01909-2
   PubMedGoogle Scholar
• Wang T, Luo M, Berrios KN, et al. Bisulfite-Free Sequencing of 5-Hydroxymethylcytosine with APOBEC-Coupled Epigenetic Sequencing (ACE-Seq). Methods Mol Biol. 2021;2198:194–201.
   Google Scholar
• Vrooman LA, Rhon-Calderon EA, Suri KV, et al. Placental abnormalities are Associated with Specific Windows of Embryo Culture in a mouse Model. Front Cell Dev Biol. 2022;10:884088. doi: 10.3389/fcell.2022.884088
   PubMed Web of Science ®Google Scholar
• Mani S, Ghosh J, Rhon-Calderon EA, et al. Embryo cryopreservation leads to sex-specific DNA methylation perturbations in both human and mouse placentas. Hum Mol Genet. 2022;31(22):3855–3872. doi: 10.1093/hmg/ddac138
   PubMed Web of Science ®Google Scholar
• Wang D, Ho ES, Cotticelli MG, et al. Skin fibroblast metabolomic profiling reveals that lipid dysfunction predicts the severity of Friedreich’s ataxia. J Lipid Res. 2022;63(9):100255. doi: 10.1016/j.jlr.2022.100255
   PubMed Web of Science ®Google Scholar
• Wang S, Blair IA, C M. Analytical methods for mass spectrometry-based metabolomics studies. Adv Exp Med Biol. 2019;1140:3–12.
   Web of Science ®Google Scholar
• Pang Z, Chong J, Zhou G, et al. MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 2021;49(W1):W388–W396. doi: 10.1093/nar/gkab382
   PubMed Web of Science ®Google Scholar
• Information, I. Scientific T. XcaliburTM 4.3 Release Notes. 2019;XCALI-98088:1–6.
   Google Scholar
• Zhou W, Triche TJ, Laird PW, et al. SeSAMe: reducing artifactual detection of DNA methylation by infinium BeadChips in genomic deletions. Nucleic Acids Res. 2018;46:1–15. doi:10.1093/nar/gky691
   PubMed Web of Science ®Google Scholar
• Larsson J, Godfrey J, Gustafsson P, et al. eulerr: Area-Proportional Euler and Venn Diagrams with Ellipses. CRAN. 2024. https://jolars.github.io/eulerr/
   Google Scholar
• Yu G, Wang LG, Han Y, et al. ClusterProfiler: an R package for comparing biological themes among gene clusters. Omics J Integr Biol. 2012;16(5):284–287. doi: 10.1089/omi.2011.0118
   PubMed Web of Science ®Google Scholar
• Dobin A, Davis CA, Schlesinger F, et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15–21. doi: 10.1093/bioinformatics/bts635
   PubMed Web of Science ®Google Scholar
• Li H, Handsaker B, Wysoker A, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25(16):2078–2079. doi: 10.1093/bioinformatics/btp352
   PubMed Web of Science ®Google Scholar
• Pertea M, Pertea GM, Antonescu CM, et al. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol. 2015;33(3):290–295. doi: 10.1038/nbt.3122
   PubMed Web of Science ®Google Scholar
• Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):1–21. doi: 10.1186/s13059-014-0550-8
   Web of Science ®Google Scholar
• Heiss JA, Brennan KJ, Baccarelli AA, et al. Battle of epigenetic proportions: comparing Illumina’s EPIC methylation microarrays and TruSeq targeted bisulfite sequencing. Epigenetics. 2020;15(1–2):174–182. doi: 10.1080/15592294.2019.1656159
   PubMed Web of Science ®Google Scholar
• Zhou L, Ng HK, Drautz-Moses DI, et al. Systematic evaluation of library preparation methods and sequencing platforms for high-throughput whole genome bisulfite sequencing. Sci Rep. 2019;9(1):1–17. doi: 10.1038/s41598-019-46875-5
   PubMedGoogle Scholar
• Martin EM, Grimm SA, Xu Z, et al. Beadchip technology to detect DNA methylation in mouse faithfully recapitulates whole-genome bisulfite sequencing. Epigenomics. 2023;15(3):115–129. doi: 10.2217/epi-2023-0034
   PubMed Web of Science ®Google Scholar
• Schutsky E, DeNizio JE, Hu P, et al. Nondestructive, base-resolution sequencing of 5-hydroxymethylcytosine using a DNA deaminase. Nat Biotechnol. 2018;36(11):1083–1090. doi: 10.1038/nbt.4204
   Web of Science ®Google Scholar
• Wagner M, Steinbacher J, Kraus TFJ, et al. Age-Dependent Levels of 5-Methyl-, 5-Hydroxymethyl-, and 5-Formylcytosine in Human and Mouse Brain Tissues. Angew Chem - Int Ed. 2015;54(42):12511–12514. doi: 10.1002/anie.201502722
   PubMed Web of Science ®Google Scholar
• Szulwach KE, Li X, Li Y, et al. 5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci. 2011;14(12):1607–1616. doi: 10.1038/nn.2959
   PubMed Web of Science ®Google Scholar
• de la Rica L, Deniz Ö, Cheng KCL, et al. TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells. Genome Biol. 2016;17(1):1–14. doi: 10.1186/s13059-016-1096-8
   PubMedGoogle Scholar
• Stolz P, Mantero AS, Tvardovskiy A, et al. TET1 regulates gene expression and repression of endogenous retroviruses independent of DNA demethylation. Nucleic Acids Res. 2022;50(15):8491–8511. doi: 10.1093/nar/gkac642
   PubMed Web of Science ®Google Scholar
• Van Der Veer BK, Chen L, Custers C, et al. Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation. Nucleic Acids Res. 2023;51(11):5469–5498. doi: 10.1093/nar/gkad231
   PubMed Web of Science ®Google Scholar
• Yuita H, López-Moyado IF, Jeong H, et al. Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch. Proc Natl Acad Sci. 2023;120(6). doi: 10.1073/pnas.2214824120
   PubMed Web of Science ®Google Scholar
• Putiri EL, Tiedemann RL, Thompson JJ, et al. Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells. Genome Biol. 2014;15(6):1–20. doi: 10.1186/gb-2014-15-6-r81
   Web of Science ®Google Scholar
• Hahn MA, Qiu R, Wu X, et al. Dynamics of 5-Hydroxymethylcytosine and chromatin marks in Mammalian Neurogenesis. Cell Rep. 2013;3(2):291–300. doi: 10.1016/j.celrep.2013.01.011
   PubMed Web of Science ®Google Scholar
• Hahn MA, Szabó PE, Pfeifer GP. 5-Hydroxymethylcytosine: A stable or transient DNA modification? Genomics. 2014;104(5):314–323. doi: 10.1016/j.ygeno.2014.08.015
   PubMed Web of Science ®Google Scholar
• MacArthur IC, Dawlaty MM. TET enzymes and 5-hydroxymethylcytosine in neural progenitor cell biology and neurodevelopment. Front Cell Dev Biol. 2021;9:1–8. doi:10.3389/fcell.2021.645335
   Web of Science ®Google Scholar
• He XB, Kim M, Kim S-Y, et al. Vitamin C facilitates dopamine neuron differentiation in fetal midbrain through TET1- and JMJD3-dependent epigenetic control manner. Stem Cells. 2015;33(4):1320–1332. doi: 10.1002/stem.1932
   PubMed Web of Science ®Google Scholar
• Wu H, D’Alessio AC, Ito S, et al. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature. 2011;473(7347):389–393. doi: 10.1038/nature09934
   PubMed Web of Science ®Google Scholar
• Mikkelsen TS, Ku M, Jaffe DB, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007;448(7153):553–560. doi: 10.1038/nature06008
   PubMed Web of Science ®Google Scholar
• Wu F, Li X, Looso M, et al. Spurious transcription causing innate immune responses is prevented by 5-hydroxymethylcytosine. Nature Genet. 2023;55(1):100–111. doi: 10.1038/s41588-022-01252-3
   PubMed Web of Science ®Google Scholar
• Tsagaratou A, Lio CWJ, Yue X, et al. TET methylcytosine oxidases in T cell and B cell development and function. Front Immunol. 2017;8:1–15. doi: 10.3389/fimmu.2017.00220
   PubMed Web of Science ®Google Scholar
• Thomson JP, Hunter JM, Nestor CE, et al. Comparative analysis of affinity-based 5-hydroxymethylation enrichment techniques. Nucleic Acids Res. 2013;41(22):e206–e206. doi: 10.1093/nar/gkt1080
   PubMed Web of Science ®Google Scholar
• Lio CWJ, Rao A. TET enzymes and 5hMC in adaptive and innate immune systems. Front Immunol. 2019;10:1–13. doi: 10.3389/fimmu.2019.00210
   PubMed Web of Science ®Google Scholar
• Cui XL, Nie J, Ku J, et al. A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation. Nat Commun. 2020;11(1):1–11. doi: 10.1038/s41467-020-20001-w
   PubMed Web of Science ®Google Scholar
• Mellén M, Ayata P, Dewell S, et al. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012;151(7):1417–1430. doi: 10.1016/j.cell.2012.11.022
   PubMed Web of Science ®Google Scholar
• Leung SK, Jeffries AR, Castanho I, et al. Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing. Cell Rep. 2021;37(7):110022. doi: 10.1016/j.celrep.2021.110022
   PubMed Web of Science ®Google Scholar
• Wang X, Yu H, Gao R, et al. A comprehensive review of the family of very-long-chain fatty acid elongases: structure, function, and implications in physiology and pathology. Eur J Med Res. 2023;28(1):1–12. doi: 10.1186/s40001-023-01523-7
   PubMed Web of Science ®Google Scholar
• Yamashita A, Hayashi Y, Nemoto-Sasaki Y, et al. Acyltransferases and transacylases that determine the fatty acid composition of glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells and model organisms. Prog Lipid Res. 2014;53:18–81. doi: 10.1016/j.plipres.2013.10.001
   PubMed Web of Science ®Google Scholar
• Shindou H, Shimizu T. Acyl-CoA: lysophospholipid acyltransferases. J Biol Chem. 2009;284(1):1–5. doi: 10.1074/jbc.R800046200
   PubMed Web of Science ®Google Scholar
• Singh AB, Kan CFK, Kraemer FB, et al. Liver-specific knockdown of long-chain acyl-CoA synthetase 4 reveals its key role in VLDL-TG metabolism and phospholipid synthesis in mice fed a high-fat diet. Am J Physiol - Endocrinol Metab. 2019;316(5):E880–E894. doi: 10.1152/ajpendo.00503.2018
   PubMed Web of Science ®Google Scholar
• Rodencal J, Dixon SJ. A tale of two lipids: lipid unsaturation commands ferroptosis sensitivity. Proteomics. 2023;23(6):1–14. doi: 10.1002/pmic.202100308
   Web of Science ®Google Scholar
• Kim JW, Lee JY, Oh M, et al. An integrated view of lipid metabolism in ferroptosis revisited via lipidomic analysis. Exp Mol Med. 2023;55(8):1620–1631. doi: 10.1038/s12276-023-01077-y
   PubMed Web of Science ®Google Scholar
• He M, Kuk ACY, Ding M, et al. Spns1 is a lysophospholipid transporter mediating lysosomal phospholipid salvage. Proc Natl Acad Sci USA. 2022;119(40). doi: 10.1073/pnas.2210353119
   Web of Science ®Google Scholar
• Zhang YZ, Sui X, Xu Y, et al. NLRP3 inflammasome and lipid metabolism analysis based on UPLC-Q-TOF-MS in gouty nephropathy. Int J Mol Med. 2019;44:172–184. doi: 10.3892/ijmm.2019.4176
   PubMed Web of Science ®Google Scholar
• Hishikawa D, Hashidate T, Shimizu T, et al. Diversity and function of membrane glycerophospholipids generated by the remodeling pathway in mammalian cells. J Lipid Res. 2014;55(5):799–807. doi: 10.1194/jlr.R046094
   PubMed Web of Science ®Google Scholar
• Bowman ER, Kulkarni M, Gabriel J, et al. Altered Lipidome Composition Is Related to markers of monocyte and immune activation in antiretroviral therapy treated human immunodeficiency virus (HIV) infection and in uninfected persons. Front Immunol. 2019;10:785. doi: 10.3389/fimmu.2019.00785
   PubMed Web of Science ®Google Scholar
• Oestvang J, Anthonsen MW, Johansen B. LysoPC and PAF Trigger Arachidonic Acid Release by Divergent Signaling Mechanisms in Monocytes. J Lipids. 2011;2011:1–11. doi: 10.1155/2011/532145
   Google Scholar
• Rong X, Albert C, Hong C, et al. LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition. Cell Metab. 2013;18(5):685–697. doi: 10.1016/j.cmet.2013.10.002
   PubMed Web of Science ®Google Scholar
• Higgins AJ, Lees P. The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti‐inflammatory drugs. Equine Vet J. 1984;16(3):163–175. doi: 10.1111/j.2042-3306.1984.tb01893.x
   PubMed Web of Science ®Google Scholar
• Tallima H, El Ridi R. Arachidonic acid: physiological roles and potential health benefits – a review. J Adv Res. 2018;11:33–41. doi:10.1016/j.jare.2017.11.004
   PubMed Web of Science ®Google Scholar
• Calder PC. Omega-3 fatty acids and inflammatory processes. Nutrients. 2010;2(3):355–374. doi: 10.3390/nu2030355
   PubMed Web of Science ®Google Scholar
• Yu H, Su Y, Shin J, et al. Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair. Nat Neurosci. 2015;18(6):836–843. doi: 10.1038/nn.4008
   PubMed Web of Science ®Google Scholar
• Greer CB, Wright J, Weiss JD, et al. Tet1 isoforms differentially regulate gene expression, synaptic transmission, and memory in the mammalian brain. J Neurosci. 2021;41(4):578–593. doi: 10.1523/JNEUROSCI.1821-20.2020
   PubMed Web of Science ®Google Scholar
• Hahn MA, Qiu R, Wu X, et al. Report Dynamics of 5-Hydroxymethylcytosine and Chromatin Marks in Mammalian Neurogenesis. CellReports. 2013;3(2):291–300. doi: 10.1016/j.celrep.2013.01.011
   Google Scholar
• Khoueiry R, Sohni A, Thienpont B, et al. Lineage-specific functions of TET1 in the postimplantation mouse embryo. Nat Genet. 2017;49(7):1061–1072. doi: 10.1038/ng.3868
   PubMed Web of Science ®Google Scholar
• Xiong J, Zhang Z, Chen J, et al. Cooperative action between SALL4A and TET proteins in stepwise oxidation of 5-Methylcytosine. Mol Cell. 2016;64(5):913–925. doi: 10.1016/j.molcel.2016.10.013
   PubMed Web of Science ®Google Scholar
• Mulholland CB, Traube FR, Ugur E, et al. Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency. Sci Rep. 2020;10(1):1–12. doi: 10.1038/s41598-020-68600-3
   PubMed Web of Science ®Google Scholar
• Hrit J, Goodrich L, Li C, et al. OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development. Elife. 2018:e34870 1–23.
   Google Scholar
• Zheng Z, Ambigapathy G, Keifer J. MeCP2 regulates Tet1-catalyzed demethylation, CTCF binding, and learning-dependent alternative splicing of the BDNF gene in Turtle. Elife. 2017;6:1–22. doi:10.7554/eLife.25384
   Web of Science ®Google Scholar
• Cheng Y, Sun M, Chen L, et al. Ten-eleven translocation proteins modulate the response to environmental stress in mice. Cell Rep. 2018;25(11):3194–3203.e4. doi: 10.1016/j.celrep.2018.11.061
   PubMed Web of Science ®Google Scholar
• Kim H, Kang Y, Li Y, et al. Ten-eleven translocation protein 1 modulates medulloblastoma progression. Genome Biol. 2021;22(1):1–25. doi: 10.1186/s13059-021-02352-9
   PubMed Web of Science ®Google Scholar
• Ehrlich M, Ehrlich KC. DNA cytosine methylation and hydroxymethylation at the borders. Epigenomics. 2014;6(6):563–566. doi: 10.2217/epi.14.48
   PubMed Web of Science ®Google Scholar
• Kim H, Jang WY, Kang M-C, et al. TET1 contributes to neurogenesis onset time during fetal brain development in mice. Biochem Biophys Res Commun. 2016;471(4):437–443. doi: 10.1016/j.bbrc.2016.02.060
   PubMed Web of Science ®Google Scholar
• Hashimoto H, Pais JE, Dai N, et al. Structure of naegleria tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA. Nucleic Acids Res. 2015;43(22):10713–10721. doi: 10.1093/nar/gkv870
   PubMed Web of Science ®Google Scholar
• Tamanaha E, Guan S, Marks K, et al. Distributive processing by the Iron(II)/α-Ketoglutarate-dependent Catalytic Domains of the TET Enzymes Is Consistent with epigenetic roles for oxidized 5-methylcytosine bases. J Am Chem Soc. 2016;138(30):9345–9348. doi: 10.1021/jacs.6b03243
   PubMed Web of Science ®Google Scholar
• Xu L, Chen Y-C, Chong J, et al. Pyrene‐Based quantitative detection of the 5‐Formylcytosine loci symmetry in the CpG duplex content during TET‐Dependent demethylation. Angew Chem. 2014;126(42):11405–11409. doi: 10.1002/ange.201406220
   Google Scholar
• An J, Rao A, Ko M. TET family dioxygenases and DNA demethylation in stem cells and cancers. Exp Mol Med. 2017;49(4):e323–e323. doi: 10.1038/emm.2017.5
   PubMedGoogle Scholar
• Bachman M, Uribe-Lewis S, Yang X, et al. 5-hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem. 2014;6(12):1049–1055. doi: 10.1038/nchem.2064
   PubMed Web of Science ®Google Scholar
• Wheldon LM, Abakir A, Ferjentsik Z, et al. Transient accumulation of 5-carboxylcytosine indicates involvement of active demethylation in lineage specification of neural stem cells. Cell Rep. 2014;7(5):1353–1361. doi: 10.1016/j.celrep.2014.05.003
   PubMed Web of Science ®Google Scholar
• Bowles KR, Julia TCW, Qian L, et al. Reduced variability of neural progenitor cells and improved purity of neuronal cultures using magnetic activated cell sorting. PLOS ONE. 2019;14(3):1–18. doi: 10.1371/journal.pone.0213374
   Web of Science ®Google Scholar
• Shayevitch R, Askayo D, Keydar I, et al. The importance of DNA methylation of exons on alternative splicing. RNA. 2018;24(10):1351–1362. doi: 10.1261/rna.064865.117
   PubMed Web of Science ®Google Scholar
• Marina RJ, Sturgill D, Bailly MA, et al. TET -catalyzed oxidation of intragenic 5-methylcytosine regulates CTCF -dependent alternative splicing. Embo J. 2016;35(3):335–355. doi: 10.15252/embj.201593235
   PubMed Web of Science ®Google Scholar
• Maunakea AK, Nagarajan RP, Bilenky M, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466(7303):253–257. doi: 10.1038/nature09165
   PubMed Web of Science ®Google Scholar
• Luco RF, Pan Q, Tominaga K, et al. Regulation of alternative splicing by histone modifications published by: american association for the advancement of science linked references are available on JSTOR for this article: regulation of alternative splicing by histone modifications. Science. 2010;327(5968):996–1000. doi: 10.1126/science.1184208
   PubMed Web of Science ®Google Scholar
• Andersson R, Enroth S, Rada-Iglesias A, et al. Nucleosomes are well positioned in exons and carry characteristic histone modifications. Genome Res. 2009;19(10):1732–1741. doi: 10.1101/gr.092353.109
   PubMed Web of Science ®Google Scholar
• Kolasinska-Zwierz P, Down T, Latorre I, et al. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet. 2009;41(3):376–381. doi: 10.1038/ng.322
   PubMed Web of Science ®Google Scholar
• Tilgner H, Nikolaou C, Althammer S, et al. Nucleosome positioning as a determinant of exon recognition. Nat Struct Mol Biol. 2009;16(9):996–1001. doi: 10.1038/nsmb.1658
   PubMed Web of Science ®Google Scholar
• Schwartz S, Meshorer E, Ast G. Chromatin organization marks exon-intron structure. Nat Struct Mol Biol. 2009;16(9):990–995. doi: 10.1038/nsmb.1659
   PubMed Web of Science ®Google Scholar
• Kornblihtt AR. Chromatin, transcript elongation and alternative splicing. Nat Struct Mol Biol. 2006;13(1):5–7. doi: 10.1038/nsmb0106-5
   PubMed Web of Science ®Google Scholar
• Farooqui AA, Horrocks LA, Farooqui T. Glycerophospholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders. Chem Phys Lipids. 2000;106(1):1–29. doi: 10.1016/S0009-3084(00)00128-6
   PubMed Web of Science ®Google Scholar
• Yoon JH, Seo Y, Jo YS, et al. Brain lipidomics: from functional landscape to clinical significance. Sci Adv. 2022;8(37):1–15. doi: 10.1126/sciadv.adc9317
   Web of Science ®Google Scholar
• Wang D, Cheng SL, Fei Q, et al. Metabolic profiling identifies phospholipids as potential serum biomarkers for schizophrenia. Psychiatry Res. 2019;272:18–29. doi: 10.1016/j.psychres.2018.12.008
   PubMed Web of Science ®Google Scholar
• Cheng D, et al. Lipid pathway alterations in parkinson’s disease primary visual cortex. PLOS ONE. 2011;6. doi: 10.1371/journal.pone.0017299
   Web of Science ®Google Scholar
• Ojo JO, Algamal M, Leary P, et al. Converging and differential brain phospholipid dysregulation in the pathogenesis of repetitive mild traumatic brain injury and Alzheimer’s disease. Front Neurosci. 2019;13:1–17. doi: 10.3389/fnins.2019.00103
   PubMed Web of Science ®Google Scholar
• Lotrich FE, Sears B, McNamara RK. Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: relationship with interleukin-6. Brain Behav Immun. 2013;31:48–53. doi:10.1016/j.bbi.2012.08.007
   PubMed Web of Science ®Google Scholar
• Nelson JR, Raskin S. The eicosapentaenoic acid: arachidonic acid ratio and its clinical utility in cardiovascular disease. Postgrad Med. 2019;131(4):268–277. doi: 10.1080/00325481.2019.1607414
   PubMed Web of Science ®Google Scholar
• Ghazali R, Mehta KJ, Bligh SA, et al. High omega arachidonic acid/docosahexaenoic acid ratio induces mitochondrial dysfunction and altered lipid metabolism in human hepatoma cells. World J Hepatol. 2020;12(3):84–98. doi: 10.4254/wjh.v12.i3.84
   PubMed Web of Science ®Google Scholar
• Kim EA, Ae Kim J, Park MH, et al. Lysophosphatidylcholine induces endothelial cell injury by nitric oxide production through oxidative stress. J Matern Fetal Neonatal Med. 2009;22(4):325–331. doi: 10.1080/14767050802556075
   PubMed Web of Science ®Google Scholar
• Henriksen JR, Andresen TL, Feldborg LN, et al. Understanding detergent effects on lipid membranes: a Model study of Lysolipids. Biophys J. 2010;98(10):2199–2205. doi: 10.1016/j.bpj.2010.01.037
   PubMed Web of Science ®Google Scholar
• Engel KM, Schiller J, Galuska CE, et al. Phospholipases and reactive oxygen species derived lipid biomarkers in healthy and Diseased Humans and animals – a focus on Lysophosphatidylcholine. Front Physiol. 2021;12:732319. doi:10.3389/fphys.2021.732319
   PubMed Web of Science ®Google Scholar
• Plemel JR, Michaels NJ, Weishaupt N, et al. Mechanisms of lysophosphatidylcholine‐induced demyelination: A primary lipid disrupting myelinopathy. Glia. 2018;66(2):327–347. doi: 10.1002/glia.23245
   PubMed Web of Science ®Google Scholar
• Allen J, Pham L, Bond ST, et al. Acute effects of single and repeated mild traumatic brain injury on levels of neurometabolites, lipids, and mitochondrial function in male rats. Front Mol Neurosci. 2023;16:1208697. doi: 10.3389/fnmol.2023.1208697
   PubMed Web of Science ®Google Scholar
• Zheng L, Xie C, Zheng J, et al. An imbalanced ratio between PC(16: 0/16: 0) and LPC(16: 0) revealed by lipidomics supports the role of the lands cycle in ischemic brain injury. J Biol Chem. 2021;296:100151. doi: 10.1074/jbc.RA120.016565
   PubMed Web of Science ®Google Scholar
• Sun Y, Lee J-H, Kim N-H, et al. Lysophosphatidylcholine-induced apoptosis in H19-7 hippocampal progenitor cells is enhanced by the upregulation of fas ligand. Biochim Biophys Acta BBA - Mol Cell Biol Lipids. 2009;1791(1):61–68. doi: 10.1016/j.bbalip.2008.09.007
   PubMed Web of Science ®Google Scholar