Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Expert Review
  • Published:

Epigenetic and epitranscriptomic regulation of axon regeneration

Molecular Psychiatry volume 28, pages 1440–1450 (2023)Cite this article

Subjects

Abstract

Effective axonal regeneration in the adult mammalian nervous system requires coordination of elevated intrinsic growth capacity and decreased responses to the inhibitory environment. Intrinsic regenerative capacity largely depends on the gene regulatory network and protein translation machinery. A failure to activate these pathways upon injury is underlying a lack of robust axon regeneration in the mature mammalian central nervous system. Epigenetics and epitranscriptomics are key regulatory mechanisms that shape gene expression and protein translation. Here, we provide an overview of different types of modifications on DNA, histones, and RNA, underpinning the regenerative competence of axons in the mature mammalian peripheral and central nervous systems. We highlight other non-neuronal cells and their epigenetic changes in determining the microenvironment for tissue repair and axon regeneration. We also address advancements of single-cell technology in charting transcriptomic and epigenetic landscapes that may further facilitate the mechanistic understanding of differential regenerative capacity in neuronal subtypes. Finally, as epigenetic and epitranscriptomic processes are commonly affected by brain injuries and psychiatric disorders, understanding their alterations upon brain injury would provide unprecedented mechanistic insights into etiology of injury-associated-psychiatric disorders and facilitate the development of therapeutic interventions to restore brain function.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Epigenetic regulation of regenerative capacity.
Fig. 2: Epitranscriptomic regulation of regenerative capacity.

Similar content being viewed by others

References

  1. Goldberg JL, Klassen MP, Hua Y, Barres BA. Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science. 2002;296:1860–4.

    Article  CAS  PubMed  Google Scholar 

  2. Blackmore M, Letourneau PC. Changes within maturing neurons limit axonal regeneration in the developing spinal cord. J Neurobiol. 2006;66:348–60.

    Article  CAS  PubMed  Google Scholar 

  3. Park KK, Liu K, Hu Y, Smith PD, Wang C, Cai B, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science. 2008;322:963–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Smith PD, Sun F, Park KK, Cai B, Wang C, Kuwako K, et al. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron. 2009;64:617–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cho Y, Sloutsky R, Naegle KM, Cavalli V. Injury-induced HDAC5 nuclear export is essential for axon regeneration. Cell. 2013;155:894–908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tedeschi A, Dupraz S, Laskowski CJ, Xue J, Ulas T, Beyer M, et al. The calcium channel subunit Alpha2delta2 suppresses axon regeneration in the adult CNS. Neuron. 2016;92:419–34.

    Article  CAS  PubMed  Google Scholar 

  7. Chandran V, Coppola G, Nawabi H, Omura T, Versano R, Huebner EA, et al. A systems-level analysis of the peripheral nerve intrinsic axonal growth program. Neuron. 2016;89:956–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yang C, Wang X, Wang J, Wang X, Chen W, Lu N, et al. Rewiring neuronal glycerolipid metabolism determines the extent of axon regeneration. Neuron. 2020;105:276–92.e275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci. 2006;7:617–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Avraham O, Deng PY, Jones S, Kuruvilla R, Semenkovich CF, Klyachko VA, et al. Satellite glial cells promote regenerative growth in sensory neurons. Nat Commun. 2020;11:4891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bellver-Landete V, Bretheau F, Mailhot B, Vallieres N, Lessard M, Janelle ME, et al. Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury. Nat Commun. 2019;10:518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Feng Y, Peng Y, Jie J, Yang Y, Yang P. The immune microenvironment and tissue engineering strategies for spinal cord regeneration. Front Cell Neurosci. 2022;16:969002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sas AR, Carbajal KS, Jerome AD, Menon R, Yoon C, Kalinski AL, et al. A new neutrophil subset promotes CNS neuron survival and axon regeneration. Nat Immunol. 2020;21:1496–505.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci. 2004;5:146–56.

    Article  CAS  PubMed  Google Scholar 

  15. Anderson MA, Burda JE, Ren Y, Ao Y, O’Shea TM, Kawaguchi R, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature. 2016;532:195–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Duan X, Qiao M, Bei F, Kim IJ, He Z, Sanes JR. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron. 2015;85:1244–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vissers C, Sinha A, Ming GL, Song H. The epitranscriptome in stem cell biology and neural development. Neurobiol Dis. 2020;146:105139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yoon KJ, Vissers C, Ming GL, Song H. Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence. J Cell Biol. 2018;217:1901–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fujita Y, Pather SR, Ming GL, Song H. 3D spatial genome organization in the nervous system: From development and plasticity to disease. Neuron. 2022;110:2902–15.

    Article  CAS  PubMed  Google Scholar 

  20. Starnawska A, Demontis D. Role of DNA methylation in mediating genetic risk of psychiatric disorders. Front Psychiatry. 2021;12:596821.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tsankova N, Renthal W, Kumar A, Nestler EJ. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci. 2007;8:355–67.

    Article  CAS  PubMed  Google Scholar 

  22. Engel M, Eggert C, Kaplick PM, Eder M, Roh S, Tietze L, et al. The role of m(6)A/m-RNA methylation in stress response regulation. Neuron. 2018;99:389–403.e389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. van Reekum R, Cohen T, Wong J. Can traumatic brain injury cause psychiatric disorders? J Neuropsychiatry Clin Neurosci. 2000;12:316–27.

    Article  PubMed  Google Scholar 

  24. Niu J, Wang B, Wang T, Zhou T. Mechanism of METTL3-mediated m6A modification in depression-induced cognitive deficits. Am J Med Genet B Neuropsychiatr Genet. 2022;189:86–99.

    Article  CAS  PubMed  Google Scholar 

  25. Dong E, Gavin DP, Chen Y, Davis J. Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients. Transl Psychiatry. 2012;2:e159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Antunes C, Da Silva JD, Guerra-Gomes S, Alves ND, Ferreira F, Loureiro-Campos E, et al. Tet3 ablation in adult brain neurons increases anxiety-like behavior and regulates cognitive function in mice. Mol Psychiatry. 2021;26:1445–57.

    Article  CAS  PubMed  Google Scholar 

  27. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006;9:519–25.

    Article  CAS  PubMed  Google Scholar 

  28. Bahari-Javan S, Varbanov H, Halder R, Benito E, Kaurani L, Burkhardt S, et al. HDAC1 links early life stress to schizophrenia-like phenotypes. Proc Natl Acad Sci USA. 2017;114:E4686–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Grippo P, Iaccarino M, Parisi E, Scarano E. Methylation of DNA in developing sea urchin embryos. J Mol Biol. 1968;36:195–208.

    Article  CAS  PubMed  Google Scholar 

  30. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B, et al. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci. 2014;17:215–22.

    Article  CAS  PubMed  Google Scholar 

  32. Breiling A, Lyko F. Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond. Epigenetics Chromatin. 2015;8:24.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Cedar H, Bergman Y. Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009;10:295–304.

    Article  CAS  PubMed  Google Scholar 

  34. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247–57.

    Article  CAS  PubMed  Google Scholar 

  35. Probst AV, Dunleavy E, Almouzni G. Epigenetic inheritance during the cell cycle. Nat Rev Mol Cell Biol. 2009;10:192–206.

    Article  CAS  PubMed  Google Scholar 

  36. He Y, Ecker JR. Non-CG methylation in the human genome. Annu Rev Genomics Hum Genet. 2015;16:55–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23:185–8.

    Article  CAS  PubMed  Google Scholar 

  38. Della Ragione F, Vacca M, Fioriniello S, Pepe G, D’Esposito M. MECP2, a multi-talented modulator of chromatin architecture. Brief Funct Genomics. 2016;15:420–31.

    PubMed  Google Scholar 

  39. Kinde B, Gabel HW, Gilbert CS, Griffith EC, Greenberg ME. Reading the unique DNA methylation landscape of the brain: Non-CpG methylation, hydroxymethylation, and MeCP2. Proc Natl Acad Sci USA. 2015;112:6800–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sharifi O, Yasui DH. The molecular functions of MeCP2 in Rett syndrome pathology. Front Genet. 2021;12:624290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF, et al. Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci USA. 2005;102:17551–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chen L, Chen K, Lavery LA, Baker SA, Shaw CA, Li W, et al. MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. Proc Natl Acad Sci USA. 2015;112:5509–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Perzel Mandell KA, Price AJ, Wilton R, Collado-Torres L, Tao R, Eagles NJ, et al. Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex. Epigenetics. 2021;16:1–13.

    Article  PubMed  Google Scholar 

  44. Ellis SE, Gupta S, Moes A, West AB, Arking DE. Exaggerated CpH methylation in the autism-affected brain. Mol Autism. 2017;8:6.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gabel HW, Kinde B, Stroud H, Gilbert CS, Harmin DA, Kastan NR, et al. Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature. 2015;522:89–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013;341:1237905.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kass SU, Pruss D, Wolffe AP. How does DNA methylation repress transcription? Trends Genet. 1997;13:444–9.

    Article  CAS  PubMed  Google Scholar 

  48. Siegfried Z, Eden S, Mendelsohn M, Feng X, Tsuberi BZ, Cedar H. DNA methylation represses transcription in vivo. Nat Genet. 1999;22:203–6.

    Article  CAS  PubMed  Google Scholar 

  49. Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, et al. Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science. 2017;356:eaaj2239.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Hu S, Wan J, Su Y, Song Q, Zeng Y, Nguyen HN, et al. DNA methylation presents distinct binding sites for human transcription factors. eLife. 2013;2:e00726.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Heberle E, Bardet AF. Sensitivity of transcription factors to DNA methylation. Essays Biochem. 2019;63:727–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Schultz MD, He Y, Whitaker JW, Hariharan M, Mukamel EA, Leung D, et al. Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 2015;523:212–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ziller MJ, Gu H, Muller F, Donaghey J, Tsai LT, Kohlbacher O, et al. Charting a dynamic DNA methylation landscape of the human genome. Nature. 2013;500:477–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Morselli M, Pastor WA, Montanini B, Nee K, Ferrari R, Fu K, et al. In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse. Elife. 2015;4:e06205.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wu H, Coskun V, Tao J, Xie W, Ge W, Yoshikawa K, et al. Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science. 2010;329:444–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cholewa-Waclaw J, Shah R, Webb S, Chhatbar K, Ramsahoye B, Pusch O, et al. Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic. Proc Natl Acad Sci USA. 2019;116:14995–15000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Luo C, Hajkova P, Ecker JR. Dynamic DNA methylation: In the right place at the right time. Science. 2018;361:1336–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Guo JU, Su Y, Zhong C, Ming GL, Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011;145:423–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333:1303–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ito S, D’Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010;466:1129–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333:1300–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet. 2017;18:517–34.

    Article  CAS  PubMed  Google Scholar 

  63. Cui XL, Nie J, Ku J, Dougherty U, West-Szymanski DC, Collin F, et al. A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation. Nat Commun. 2020;11:6161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. He B, Zhang C, Zhang X, Fan Y, Zeng H, Liu J, et al. Tissue-specific 5-hydroxymethylcytosine landscape of the human genome. Nat Commun. 2021;12:4249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hahn MA, Qiu R, Wu X, Li AX, Zhang H, Wang J, et al. Dynamics of 5-hydroxymethylcytosine and chromatin marks in Mammalian neurogenesis. Cell Rep. 2013;3:291–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mellen 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:E7812–E7821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Tan L, Xiong L, Xu W, Wu F, Huang N, Xu Y, et 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. 2013;41:e84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Gontier G, Iyer M, Shea JM, Bieri G, Wheatley EG, Ramalho-Santos M, et al. Tet2 rescues age-related regenerative decline and enhances cognitive function in the adult mouse brain. Cell Rep. 2018;22:1974–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. van den Oord C, Copeland WE, Zhao M, Xie LY, Aberg KA, van den Oord E. DNA methylation signatures of childhood trauma predict psychiatric disorders and other adverse outcomes 17 years after exposure. Mol Psychiatry. 2022;27:3367–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Muller D, Grevet EH, Figueira da Silva NA, Bandeira CE, Barbosa E, Vitola ES, et al. Global DNA methylation changes in adults with attention deficit-hyperactivity disorder and its comorbidity with bipolar disorder: links with polygenic scores. Mol Psychiatry. 2022;27:2485–91.

    Article  CAS  PubMed  Google Scholar 

  71. Bundo M, Ueda J, Nakachi Y, Kasai K, Kato T, Iwamoto K. Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder. Mol Psychiatry. 2021;26:3407–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cheng Y, Li Z, Manupipatpong S, Lin L, Li X, Xu T, et al. 5-Hydroxymethylcytosine alterations in the human postmortem brains of autism spectrum disorder. Hum Mol Genet. 2018;27:2955–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Golzenleuchter M, Kanwar R, Zaibak M, Al Saiegh F, Hartung T, Klukas J, et al. Plasticity of DNA methylation in a nerve injury model of pain. Epigenetics. 2015;10:200–12.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Garriga J, Laumet G, Chen SR, Zhang Y, Madzo J, Issa JJ, et al. Nerve injury-induced chronic pain is associated with persistent DNA methylation reprogramming in dorsal root ganglion. J Neurosci. 2018;38:6090–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Iskandar BJ, Rizk E, Meier B, Hariharan N, Bottiglieri T, Finnell RH, et al. Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation. J Clin Investig. 2010;120:1603–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Madrid A, Borth LE, Hogan KJ, Hariharan N, Papale LA, Alisch RS, et al. DNA methylation and hydroxymethylation have distinct genome-wide profiles related to axonal regeneration. Epigenetics. 2021;16:64–78.

    Article  PubMed  Google Scholar 

  77. Oh YM, Mahar M, Ewan EE, Leahy KM, Zhao G, Cavalli V. Epigenetic regulator UHRF1 inactivates REST and growth suppressor gene expression via DNA methylation to promote axon regeneration. Proc Natl Acad Sci USA. 2018;115:E12417–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Li H, Rauch T, Chen ZX, Szabo PE, Riggs AD, Pfeifer GP. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem. 2006;281:19489–500.

    Article  CAS  PubMed  Google Scholar 

  79. Rajavelu A, Lungu C, Emperle M, Dukatz M, Brohm A, Broche J, et al. Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2. Nucleic Acids Res. 2018;46:9044–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Loh YE, Koemeter-Cox A, Finelli MJ, Shen L, Friedel RH, Zou H. Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration. Epigenetics. 2017;12:77–92.

    Article  PubMed  Google Scholar 

  81. Weng YL, An R, Cassin J, Joseph J, Mi R, Wang C, et al. An intrinsic epigenetic barrier for functional axon regeneration. Neuron. 2017;94:337–346.e336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Liu XS, Jaenisch R. Editing the epigenome to tackle brain disorders. Trends Neurosci. 2019;42:861–70.

    Article  CAS  PubMed  Google Scholar 

  83. Thakore PI, Black JB, Hilton IB, Gersbach CA. Editing the epigenome: technologies for programmable transcription and epigenetic modulation. Nat Methods. 2016;13:127–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hilton IB, D’Ippolito AM, Vockley CM, Thakore PI, Crawford GE, Reddy TE, et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol. 2015;33:510–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Liu XS, Wu H, Ji X, Stelzer Y, Wu X, Czauderna S, et al. Editing DNA methylation in the mammalian genome. Cell. 2016;167:233–47.e217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Liu XS, Wu H, Krzisch M, Wu X, Graef J, Muffat J, et al. Rescue of fragile X syndrome neurons by DNA methylation editing of the FMR1 Gene. Cell. 2018;172:979–92.e976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Gasperini M, Hill AJ, McFaline-Figueroa JL, Martin B, Kim S, Zhang MD, et al. A genome-wide framework for mapping gene regulation via cellular genetic screens. Cell. 2019;176:377–90.e319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci USA. 2010;107:21931–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129:823–37.

    Article  CAS  PubMed  Google Scholar 

  90. Padeken J, Methot SP, Gasser SM. Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance. Nat Rev Mol Cell Biol. 2022;23:623–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Sun H, Kennedy PJ, Nestler EJ. Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacology. 2013;38:124–37.

    Article  CAS  PubMed  Google Scholar 

  92. Kishi T, Yoshimura R, Kitajima T, Okochi T, Okumura T, Tsunoka T, et al. SIRT1 gene is associated with major depressive disorder in the Japanese population. J Affect Disord. 2010;126:167–73.

    Article  CAS  PubMed  Google Scholar 

  93. Puttagunta R, Tedeschi A, Soria MG, Hervera A, Lindner R, Rathore KI, et al. PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system. Nat Commun. 2014;5:3527.

    Article  PubMed  Google Scholar 

  94. Lv L, Han X, Sun Y, Wang X, Dong Q. Valproic acid improves locomotion in vivo after SCI and axonal growth of neurons in vitro. Exp Neurol. 2012;233:783–90.

    Article  CAS  PubMed  Google Scholar 

  95. Finelli MJ, Wong JK, Zou H. Epigenetic regulation of sensory axon regeneration after spinal cord injury. J Neurosci. 2013;33:19664–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kaya-Okur HS, Wu SJ, Codomo CA, Pledger ES, Bryson TD, Henikoff JG, et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat Commun. 2019;10:1930.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Skene PJ, Henikoff S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife. 2017;6:e21856.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Balsalobre A, Drouin J. Pioneer factors as master regulators of the epigenome and cell fate. Nat Rev Mol Cell Biol. 2022;23:449–64.

    Article  CAS  PubMed  Google Scholar 

  99. Wapinski OL, Vierbuchen T, Qu K, Lee QY, Chanda S, Fuentes DR, et al. Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell. 2013;155:621–35.

    Article  CAS  PubMed  Google Scholar 

  100. Su Y, Shin J, Zhong C, Wang S, Roychowdhury P, Lim J, et al. Neuronal activity modifies the chromatin accessibility landscape in the adult brain. Nat Neurosci. 2017;20:476–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Barbon A, Magri C. RNA editing and modifications in mood disorders. Genes. 2020;11:872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Widagdo J, Anggono V. The m6A-epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity. J Neurochem. 2018;147:137–52.

    Article  CAS  PubMed  Google Scholar 

  103. Abe N, Borson SH, Gambello MJ, Wang F, Cavalli V. Mammalian target of rapamycin (mTOR) activation increases axonal growth capacity of injured peripheral nerves. J Biol Chem. 2010;285:28034–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, et al. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci. 2010;13:1075–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Barbieri I, Kouzarides T. Role of RNA modifications in cancer. Nat Rev Cancer. 2020;20:303–22.

    Article  CAS  PubMed  Google Scholar 

  106. Roundtree IA, Evans ME, Pan T, He C. Dynamic RNA modifications in gene expression regulation. Cell. 2017;169:1187–1200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Eyler DE, Franco MK, Batool Z, Wu MZ, Dubuke ML, Dobosz-Bartoszek M, et al. Pseudouridinylation of mRNA coding sequences alters translation. Proc Natl Acad Sci USA. 2019;116:23068–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Schumann U, Zhang HN, Sibbritt T, Pan A, Horvath A, Gross S, et al. Multiple links between 5-methylcytosine content of mRNA and translation. BMC Biol. 2020;18:40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, et al. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 2015;161:1388–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Liu J, Yue Y, Han D, Wang X, Fu Y, Zhang L, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014;10:93–95.

    Article  CAS  PubMed  Google Scholar 

  111. Yue Y, Liu J, Cui X, Cao J, Luo G, Zhang Z, et al. VIRMA mediates preferential m(6)A mRNA methylation in 3’UTR and near stop codon and associates with alternative polyadenylation. Cell Discov. 2018;4:10.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Wen J, Lv R, Ma H, Shen H, He C, Wang J, et al. Zc3h13 regulates nuclear RNA m(6)A methylation and mouse embryonic stem cell self-renewal. Mol Cell. 2018;69:1028–38.e1026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ping XL, Sun BF, Wang L, Xiao W, Yang X, Wang WJ, et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 2014;24:177–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Xu H, Dzhashiashvili Y, Shah A, Kunjamma RB, Weng YL, Elbaz B, et al. m(6)A mRNA methylation is essential for oligodendrocyte maturation and CNS myelination. Neuron. 2020;105:293–309.e295.

    Article  CAS  PubMed  Google Scholar 

  115. Yoon KJ, Ringeling FR, Vissers C, Jacob F, Pokrass M, Jimenez-Cyrus D, et al. Temporal control of mammalian cortical neurogenesis by m(6)A methylation. Cell. 2017;171:877–89.e817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Alarcon CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF. HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell. 2015;162:1299–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Huang H, Weng H, Sun W, Qin X, Shi H, Wu H, et al. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018;20:285–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Roundtree IA, Luo GZ, Zhang Z, Wang X, Zhou T, Cui Y, et al. YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife. 2017;6:e31311.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2014;505:117–20.

    Article  PubMed  Google Scholar 

  120. Zhou KI, Shi H, Lyu R, Wylder AC, Matuszek Z, Pan JN, et al. Regulation of co-transcriptional pre-mRNA Splicing by m(6)A through the low-complexity protein hnRNPG. Mol Cell. 2019;76:70–81.e79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Weng YL, Wang X, An R, Cassin J, Vissers C, Liu Y, et al. Epitranscriptomic m(6)A regulation of axon regeneration in the adult mammalian nervous system. Neuron. 2018;97:313–25.e316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Flamand MN, Meyer KD. m6A and YTHDF proteins contribute to the localization of select neuronal mRNAs. Nucleic Acids Res. 2022;50:4464–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Yu J, Chen M, Huang H, Zhu J, Song H, Zhu J, et al. Dynamic m6A modification regulates local translation of mRNA in axons. Nucleic Acids Res. 2018;46:1412–23.

    Article  CAS  PubMed  Google Scholar 

  124. Terenzio M, Koley S, Samra N, Rishal I, Zhao Q, Sahoo PK, et al. Locally translated mTOR controls axonal local translation in nerve injury. Science. 2018;359:1416–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Villa E, Sahu U, O’Hara BP, Ali ES, Helmin KA, Asara JM, et al. mTORC1 stimulates cell growth through SAM synthesis and m(6)A mRNA-dependent control of protein synthesis. Mol Cell. 2021;81:2076.e2079.

    Article  Google Scholar 

  126. Sun HL, Zhu AC, Gao Y, Terajima H, Fei Q, Liu S, et al. Stabilization of ERK-phosphorylated METTL3 by USP5 increases m(6)A methylation. Mol Cell. 2020;80:633–47.e637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Bertero A, Brown S, Madrigal P, Osnato A, Ortmann D, Yiangou L, et al. The SMAD2/3 interactome reveals that TGFbeta controls m(6)A mRNA methylation in pluripotency. Nature. 2018;555:256–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Du Y, Hou G, Zhang H, Dou J, He J, Guo Y, et al. SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function. Nucleic Acids Res. 2018;46:5195–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Pinto R, Vagbo CB, Jakobsson ME, Kim Y, Baltissen MP, O’Donohue MF, et al. The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. Nucleic Acids Res. 2020;48:830–46.

    Article  CAS  PubMed  Google Scholar 

  130. Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C, Humphreys P, et al. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J. 2014;33:2020–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Liu F, Clark W, Luo G, Wang X, Fu Y, Wei J, et al. ALKBH1-mediated tRNA demethylation regulates translation. Cell. 2016;167:816–28.e816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Tuorto F, Liebers R, Musch T, Schaefer M, Hofmann S, Kellner S, et al. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. 2012;19:900–5.

    Article  CAS  PubMed  Google Scholar 

  133. Levi O, Arava YS. Pseudouridine-mediated translation control of mRNA by methionine aminoacyl tRNA synthetase. Nucleic Acids Res. 2021;49:432–43.

    Article  CAS  PubMed  Google Scholar 

  134. Zhang F, Yoon K, Zhang DY, Kim NS, Ming GL, Song H. Epitranscriptomic regulation of cortical neurogenesis via Mettl8-dependent mitochondrial tRNA m(3)C modification. Cell Stem Cell. 2023;30:300–11.e311.

    Article  CAS  PubMed  Google Scholar 

  135. Ontiveros RJ, Shen H, Stoute J, Yanas A, Cui Y, Zhang Y, et al. Coordination of mRNA and tRNA methylations by TRMT10A. Proc Natl Acad Sci USA. 2020;117:7782–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Greenhalgh AD, David S, Bennett FC. Immune cell regulation of glia during CNS injury and disease. Nat Rev Neurosci. 2020;21:139–52.

    Article  CAS  PubMed  Google Scholar 

  137. Jakel S, Dimou L. Glial cells and their function in the adult brain: a journey through the history of their ablation. Front Cell Neurosci. 2017;11:24.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Reed CB, Feltri ML, Wilson ER. Peripheral glia diversity. J Anat. 2022;24:1219–34.

    Article  Google Scholar 

  139. Li C, Wu Z, Zhou L, Shao J, Hu X, Xu W, et al. Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury. Signal Transduct Target Ther. 2022;7:65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Faraco G, Pittelli M, Cavone L, Fossati S, Porcu M, Mascagni P, et al. Histone deacetylase (HDAC) inhibitors reduce the glial inflammatory response in vitro and in vivo. Neurobiol Dis. 2009;36:269–79.

    Article  CAS  PubMed  Google Scholar 

  141. Suh HS, Choi S, Khattar P, Choi N, Lee SC. Histone deacetylase inhibitors suppress the expression of inflammatory and innate immune response genes in human microglia and astrocytes. J Neuroimmune Pharmacol. 2010;5:521–32.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Popovich PG, Jones TB. Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics. Trends Pharmacol Sci. 2003;24:13–17.

    Article  CAS  PubMed  Google Scholar 

  143. Zhou X, Wahane S, Friedl MS, Kluge M, Friedel CC, Avrampou K, et al. Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2. Nat Neurosci. 2020;23:337–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Li Y, He X, Kawaguchi R, Zhang Y, Wang Q, Monavarfeshani A, et al. Microglia-organized scar-free spinal cord repair in neonatal mice. Nature. 2020;587:613–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Ayata P, Badimon A, Strasburger HJ, Duff MK, Montgomery SE, Loh YE, et al. Epigenetic regulation of brain region-specific microglia clearance activity. Nat Neurosci. 2018;21:1049–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Duncan GJ, Manesh SB, Hilton BJ, Assinck P, Plemel JR, Tetzlaff W. The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury. Glia. 2020;68:227–45.

    Article  PubMed  Google Scholar 

  147. Gregath A, Lu QR. Epigenetic modifications-insight into oligodendrocyte lineage progression, regeneration, and disease. FEBS Lett. 2018;592:1063–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Wahane S, Zhou X, Zhou X, Guo L, Friedl MS, Kluge M, et al. Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity. Sci Adv. 2021;7:eabd8811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Kuboyama T, Wahane S, Huang Y, Zhou X, Wong JK, Koemeter-Cox A, et al. HDAC3 inhibition ameliorates spinal cord injury by immunomodulation. Sci Rep. 2017;7:8641.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Bailey ZS, Grinter MB, VandeVord PJ. Astrocyte reactivity following blast exposure involves aberrant histone acetylation. Front Mol Neurosci. 2016;9:64.

    Article  PubMed  PubMed Central  Google Scholar 

  151. Zhang ZY, Zhang Z, Fauser U, Schluesener HJ. Global hypomethylation defines a sub-population of reactive microglia/macrophages in experimental traumatic brain injury. Neurosci Lett. 2007;429:1–6.

    Article  CAS  PubMed  Google Scholar 

  152. Gasparoni G, Bultmann S, Lutsik P, Kraus TFJ, Sordon S, Vlcek J, et al. DNA methylation analysis on purified neurons and glia dissects age and Alzheimer’s disease-specific changes in the human cortex. Epigenetics Chromatin. 2018;11:41.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Hung HA, Sun G, Keles S, Svaren J. Dynamic regulation of Schwann cell enhancers after peripheral nerve injury. J Biol Chem. 2015;290:6937–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Zeisel A, Munoz-Manchado AB, Codeluppi S, Lonnerberg P, La Manno G, Jureus A, et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science. 2015;347:1138–42.

    Article  CAS  PubMed  Google Scholar 

  155. Rosenberg AB, Roco CM, Muscat RA, Kuchina A, Sample P, Yao Z, et al. Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Science. 2018;360:176–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Shin J, Berg DA, Zhu Y, Shin JY, Song J, Bonaguidi MA, et al. Single-cell RNA-Seq with waterfall reveals molecular cascades underlying adult neurogenesis. Cell Stem Cell. 2015;17:360–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Lake BB, Ai R, Kaeser GE, Salathia NS, Yung YC, Liu R, et al. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science. 2016;352:1586–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Zhu C, Yu M, Huang H, Juric I, Abnousi A, Hu R, et al. An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome. Nat Struct Mol Biol. 2019;26:1063–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Zhu C, Zhang Y, Li YE, Lucero J, Behrens MM, Ren B. Joint profiling of histone modifications and transcriptome in single cells from mouse brain. Nat Methods. 2021;18:283–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Trapnell C, Cacchiarelli D, Grimsby J, Pokharel P, Li S, Morse M, et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat Biotechnol. 2014;32:381–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Stuart T, Satija R. Integrative single-cell analysis. Nat Rev Genet. 2019;20:257–72.

    Article  CAS  PubMed  Google Scholar 

  162. Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36:411–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Tuszynski Mark H, Steward O. Concepts and methods for the study of axonal regeneration in the CNS. Neuron. 2012;74:777–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Cooke P, Janowitz H, Dougherty SE. Neuronal redevelopment and the regeneration of neuromodulatory axons in the adult mammalian central nervous system. Front Cell Neurosci. 2022;16:872501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Tian F, Cheng Y, Zhou S, Wang Q, Monavarfeshani A, Gao K, et al. Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells. Neuron. 2022;110:2607–24.e2608.

    Article  CAS  PubMed  Google Scholar 

  166. Jacobi A, Tran NM, Yan W, Benhar I, Tian F, Schaffer R, et al. Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells. Neuron. 2022;110:2625–45.e2627.

    Article  CAS  PubMed  Google Scholar 

  167. Li L, Fang F, Feng X, Zhuang P, Huang H, Liu P, et al. Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes. Neuron. 2022;110:2646–63.e2646.

    Article  CAS  PubMed  Google Scholar 

  168. Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, et al. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity. 2019;50:253–71.e256.

    Article  CAS  PubMed  Google Scholar 

  169. Milich LM, Choi JS, Ryan C, Cerqueira SR, Benavides S, Yahn SL, et al. Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord. J Exp Med. 2021;218:e20210040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Hasel P, Rose IVL, Sadick JS, Kim RD, Liddelow SA. Neuroinflammatory astrocyte subtypes in the mouse brain. Nat Neurosci. 2021;24:1475–87.

    Article  CAS  PubMed  Google Scholar 

  171. Meyer KD. DART-seq: an antibody-free method for global m(6)A detection. Nat Methods. 2019;16:1275–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Tegowski M, Flamand MN, Meyer KD. scDART-seq reveals distinct m(6)A signatures and mRNA methylation heterogeneity in single cells. Mol Cell. 2022;82:868–78.e810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Kaplan GB, Leite-Morris KA, Wang L, Rumbika KK, Heinrichs SC, Zeng X, et al. Pathophysiological bases of comorbidity: traumatic brain injury and post-traumatic stress disorder. J Neurotrauma. 2018;35:210–25.

    Article  PubMed  Google Scholar 

Download references

Funding

Funding

The research in the authors’ laboratories were supported by grants from the National Institutes of Health (R35NS116843 to HS, R35NS097370 to G-lM, R01ES031511 to Y-LW), Houston Methodist Neurospark (to Y-LW), and Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to G-lM). Figures were created with BioRender.com.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Houston Methodist Neurological Institute, Houston, TX, 77030, USA

    Yating Cheng & Yi-Lan Weng

  2. Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, 77030, USA

    Yating Cheng & Yi-Lan Weng

  3. Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Hongjun Song & Guo-li Ming

  4. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Hongjun Song & Guo-li Ming

  5. The Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Hongjun Song

  6. Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Hongjun Song & Guo-li Ming

  7. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Guo-li Ming

Authors
  1. Yating Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongjun Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guo-li Ming
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi-Lan Weng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YC wrote the manuscript with contributions from all co-authors.

Corresponding authors

Correspondence to Guo-li Ming or Yi-Lan Weng.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, Y., Song, H., Ming, Gl. et al. Epigenetic and epitranscriptomic regulation of axon regeneration. Mol Psychiatry 28, 1440–1450 (2023). https://doi.org/10.1038/s41380-023-02028-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-023-02028-9

Search

Advanced search

Quick links