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http://dx.doi.org/10.14348/molcells.2017.2311

Epigenetic Regulation of Axon Regeneration after Neural Injury  

Shin, Jung Eun (The Research Institute of Basic Sciences, Seoul National University)
Cho, Yongcheol (Department of Life Sciences, Korea University)
Publication Information
Molecules and Cells / v.40, no.1, 2017 , pp. 10-16 More about this Journal
Abstract
When peripheral axons are damaged, neuronal injury signaling pathways induce transcriptional changes that support axon regeneration and consequent functional recovery. The recent development of bioinformatics techniques has allowed for the identification of many of the regeneration-associated genes that are regulated by neural injury, yet it remains unclear how global changes in transcriptome are coordinated. In this article, we review recent studies on the epigenetic mechanisms orchestrating changes in gene expression in response to nerve injury. We highlight the importance of epigenetic mechanisms in discriminating efficient axon regeneration in the peripheral nervous system and very limited axon regrowth in the central nervous system and discuss the therapeutic potential of targeting epigenetic regulators to improve neural recovery.
Keywords
axon regeneration; epigenetic regulation; histone modification; nerve injury;
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1 Bode, A.G., and Dong, Z. (2004). Post-translational modification of p53 in tumorigenesis. Nat. Rev. Cancer. 4, 793-805   DOI
2 Bomze, H.M., Bulsara, K.R., Iskandar, B.J., Caroni, P., and Skene, J.H. (2001). Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat. Neurosci. 4, 38-43.   DOI
3 Bradke, F., Fawcett, J.W., and Spira, M.E. (2012). Assembly of a new growth cone after axotomy: the precursor to axon regeneration. Nat. Rev. Neurosci. 13, 183-193.   DOI
4 Cai, D., Qiu, J., Cao, Z., McAtee, M., Bregman, B.S., and Filbin, M.T. (2001). Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J. Neurosci. 21, 4731-4739.   DOI
5 Chandran, V., Coppola, G., Nawabi, H., Omura, T., Versano, R., Huebner, E. a, Zhang, A., Costigan, M., Yekkirala, A., Barrett, L., et al. (2016). A systems-level analysis of the peripheral nerve intrinsic axonal growth program. Neuron 89, 956-970.   DOI
6 Chen, M.S., Huber, A.B., van der Haar, M.E., Frank, M., Schnell, L., Spillmann, A.A., Christ, F., and Schwab, M.E. (2000). Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403, 434-439.   DOI
7 Chen, Z.-L., Yu, W.-M., and Strickland, S. (2007). Peripheral regeneration. Annu. Rev. Neurosci. 30, 209-233.   DOI
8 Cho, Y., and Cavalli, V. (2014). HDAC signaling in neuronal development and axon regeneration. Curr. Opin. Neurobiol. 27, 118-126.
9 Stoll, G., Jander, S., and Myers, R.R. (2002). Degeneration and regeneration of the peripheral nervous system: from Augustus Waller's observations to neuroinflammation. J. Peripher. Nerv. Syst. JPNS 7, 13-27.   DOI
10 Tedeschi, A., Nguyen, T., Puttagunta, R., Gaub, P., and Di Giovanni, S. (2009). A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration. Cell Death Differ. 16, 543-554.   DOI
11 Tetzlaff, W., Alexander, S.W., Miller, F.D., and Bisby, M.A. (1991). Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43. J. Neurosci. 11, 2528-2544.   DOI
12 De Vos, K.J., Grierson, A.J., Ackerley, S., and Miller, C.C.J. (2008). Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci. 31, 151-173.   DOI
13 Wang, K.C. (2002). Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. 417, 941-944.   DOI
14 Wang, Q.J. (2006). PKD at the crossroads of DAG and PKC signaling. Trends Pharmacol. Sci. 27, 317-323.   DOI
15 Wang, M.S., Davis, A. a, Culver, D.G., and Glass, J.D. (2002). WldS mice are resistant to paclitaxel (taxol) neuropathy. Ann. Neurol. 52, 442-447.   DOI
16 Yiu, G., and He, Z. (2006). Glial inhibition of CNS axon regeneration. Nat. Rev. Neurosci. 7, 617-627.   DOI
17 Coleman, M.P., and Freeman, M.R. (2010). Wallerian degeneration, wld(s), and nmnat. Annu. Rev. Neurosci. 33, 245-267.   DOI
18 Erturk, A., Hellal, F., Enes, J., and Bradke, F. (2007). Disorganized microtubules underlie the formation of retraction bulbs and the failure of axonal regeneration. J. Neurosci. 27, 9169-9180.   DOI
19 Cho, Y., Sloutsky, R., Naegle, K.M., and Cavalli, V. (2013). Injury-induced HDAC5 nuclear export is essential for axon regeneration. Cell 155, 894-908.   DOI
20 Cho, Y., Shin, J.E., Ewan, E.E., Oh, Y.M., Pita-Thomas, W., and Cavalli, V. (2015). Activating injury-responsive genes with hypoxia enhances axon regeneration through neuronal HIF-$1{\alpha}$. Neuron 88, 720-734.   DOI
21 Finelli, M.J., Wong, J.K., and Zou, H. (2013). Epigenetic regulation of sensory axon regeneration after spinal cord injury. J. Neurosci. 33, 19664-19676.   DOI
22 Gao, Y., Deng, K., Hou, J., Bryson, J.B., Barco, A., Nikulina, E., Spencer, T., Mellado, W., Kandel, E.R., and Filbin, M.T. (2004). Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron 44, 609-621.   DOI
23 Gaub, P., Tedeschi, a, Puttagunta, R., Nguyen, T., Schmandke, a, and Di Giovanni, S. (2010). HDAC inhibition promotes neuronal outgrowth and counteracts growth cone collapse through CBP/p300 and P/CAF-dependent p53 acetylation. Cell Death Differ. 17, 1392-1408.   DOI
24 Gaub, P., Joshi, Y., Wuttke, A., Naumann, U., Schnichels, S., Heiduschka, P., and Di Giovanni, S. (2011). The histone acetyltransferase p300 promotes intrinsic axonal regeneration. Brain 134, 2134-2148.   DOI
25 Geoffroy, C.G., Meves, J.M., and Zheng, B. (2016). The age factor in axonal repair after spinal cord injury: A focus on neuron-intrinsic mechanisms. Neurosci. Lett. doi.org/10.1016/j.neulet.2016.11.003   DOI
26 Jones, P.A. (2012). Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484-492.   DOI
27 Di Giovanni, S., Knights, C.D., Rao, M., Yakovlev, A., Beers, J., Catania, J., Avantaggiati, M.L., and Faden, A.I. (2006). The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J. 25, 4084-4096.   DOI
28 Coleman, M. (2005). Axon degeneration mechanisms: commonality amid diversity. Nat. Rev. Neurosci. 6, 889-898.   DOI
29 Gong, L., Wu, J., Zhou, S., Wang, Y., Qin, J., Yu, B., Gu, X., and Yao, C. (2016). Global analysis of transcriptome in dorsal root ganglia following peripheral nerve injury in rats. Biochem. Biophys. Res. Commun. 478, 206-212.   DOI
30 Gordon, T., Tyreman, N., and Raji, M.A. (2011). The basis for diminished functional recovery after delayed peripheral nerve repair. J. Neurosci. 31, 5325-5334.   DOI
31 Kenney, a M., and Kocsis, J.D. (1998). Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia In vivo. J. Neurosci. 18, 1318-1328.   DOI
32 Kobayashi, J., Mackinnon, S.E., Watanabe, O., Ball, D.J., Gu, X.M., Hunter, D.A., and Kuzon, Jr, W.M. (1997). The effect of duration of muscle denervation on functional recovery. Muscle Nerve 20, 858-866.   DOI
33 Lee, K.K., and Workman, J.L. (2007). Histone acetyltransferase complexes: one size doesn't fit all. Nat. Rev. Mol. Cell Biol. 8, 284-295.   DOI
34 Ma, T.C., and Willis, D.E. (2015). What makes a RAG regeneration associated? Front. Mol. Neurosci. 8, 43.
35 Li, S., Xue, C., Yuan, Y., Zhang, R., Wang, Y., Wang, Y., Yu, B., Liu, J., Ding, F., Yang, Y., et al. (2015). The transcriptional landscape of dorsal root ganglia after sciatic nerve transection. Sci. Rep. 5, 16888.   DOI
36 Lindner, R., Puttagunta, R., Nguyen, T., and Di Giovanni, S. (2014). DNA methylation temporal profiling following peripheral versus central nervous system axotomy. Sci. Data 1, 140038.   DOI
37 Liu, K., Tedeschi, A., Park, K.K., and He, Z. (2011). Neuronal intrinsic mechanisms of axon regeneration. Annu. Rev. Neurosci. 34, 131-152.   DOI
38 Michaelevski, I., Segal-Ruder, Y., Rozenbaum, M., Medzihradszky, K.F., Shalem, O., Coppola, G., Horn-Saban, S., Ben-Yaakov, K., Dagan, S.Y., Rishal, I., et al. (2010). Signaling to transcription networks in the neuronal retrograde injury response. Sci. Signal. 3, ra53.
39 Magill, C.K., Tong, A., Kawamura, D., Hayashi, A., Hunter, D. a, Parsadanian, A., Mackinnon, S.E., and Myckatyn, T.M. (2007). Reinnervation of the tibialis anterior following sciatic nerve crush injury: a confocal microscopic study in transgenic mice. Exp. Neurol. 207, 64-74.   DOI
40 McKeon, R.J., Schreiber, R.C., Rudge, J.S., and Silver, J. (1991). Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with. J. Neurosci. 11, 3398-3411.   DOI
41 Mukhopadhyay, G., Doherty, P., Walsh, F.S., Crocker, P.R., and Filbin, M.T. (1994). A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13, 757-767.   DOI
42 Neumann, S., and Woolf, C.J. (1999). Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 23, 83-91.   DOI
43 Neumann, S., Bradke, F., Tessier-Lavigne, M., and Basbaum, A.I. (2002). Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 34, 885-893.   DOI
44 Pan, Y.A., Misgeld, T., Lichtman, J.W., and Sanes, J.R. (2003). Effects of neurotoxic and neuroprotective agents on peripheral nerve regeneration assayed by time-lapse imaging in vivo. J. Neurosci. 23, 11479-11488.   DOI
45 Park, K.K., Liu, K., Hu, Y., Smith, P.D., Wang, C., Cai, B., Xu, B., Connolly, L., Kramvis, I., Sahin, M., et al. (2008). Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322, 963-966.   DOI
46 Rivieccio, M.A., Brochier, C., Willis, D.E., Walker, B.A., D'Annibale, M.A., McLaughlin, K., Siddiq, A., Kozikowski, A.P., Jaffrey, S.R., Twiss, J.L., et al. (2009). HDAC6 is a target for protection and regeneration following injury in the nervous system. Proc. Natl. Acad. Sci. USA 106, 19599-19604.   DOI
47 Puttagunta, R., Tedeschi, A., Soria, M.G., Hervera, A., Lindner, R., Rathore, K.I., Gaub, P., Joshi, Y., Nguyen, T., Schmandke, A., et al. (2014). PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system. Nat. Commun. 5, 3527.   DOI
48 Qiu, J., Cai, D., Dai, H., Mcatee, M., Hoffman, P.N., Bregman, B.S., and Filbin, M.T. (2002). Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 34, 895-903.   DOI
49 Raivich, G., Bohatschek, M., Da Costa, C., Iwata, O., Galiano, M., Hristova, M., Nateri, A.S., Makwana, M., Riera-Sans, L., Wolfer, D.P., et al. (2004). The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron 43, 57-67.   DOI
50 Rishal, I., and Fainzilber, M. (2014). Axon-soma communication in neuronal injury. Nat. Rev. Neurosci. 15, 32-42.   DOI
51 Shin, J.E., Cho, Y., Beirowski, B., Milbrandt, J., Cavalli, V., and DiAntonio, A. (2012). Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron 74, 1015-1022.   DOI
52 Smith, D.S., and Skene, J.H. (1997). A transcription-dependent switch controls competence of adult neurons for distinct modes of axon growth. J. Neurosci. 17, 646-658.   DOI
53 Smith, P.D., Sun, F., Park, K.K., Cai, B., Wang, C., Kuwako, K., Martinez-Carrasco, I., Connolly, L., and He, Z. (2009). SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 64, 617-623.   DOI
54 Ben-Tov Perry, R., Doron-Mandel, E., Iavnilovitch, E., Rishal, I., Dagan, S.Y., Tsoory, M., Coppola, G., McDonald, M.K., Gomes, C., Geschwind, D.H., et al. (2012). Subcellular knockout of importin ${\beta}1$ perturbs axonal retrograde signaling. Neuron 75, 294-305.   DOI
55 Abe, N., and Cavalli, V. (2008). Nerve injury signaling. Curr. Opin. Neurobiol. 18, 276-283.   DOI
56 Abe, N., Borson, S.H., Gambello, M.J., Wang, F., and Cavalli, V. (2010). Mammalian target of rapamycin (mTOR) activation increases axonal growth capacity of injured peripheral nerves. J. Biol. Chem. 285, 28034-28043.   DOI
57 Bareyre, F.M., Garzorz, N., Lang, C., Misgeld, T., Büning, H., and Kerschensteiner, M. (2011). In vivo imaging reveals a phase-specific role of STAT3 during central and peripheral nervous system axon regeneration. Proc. Natl. Acad. Sci. USA 108, 6282-6287.   DOI