REVIEW

Reshaping the chromatin landscape after spinal cord injury

  • Jamie K. WONG 1 ,
  • Hongyan ZOU , 1,2
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  • 1. Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  • 2. Department of Neurosurgery, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA

Received date: 02 Jun 2014

Accepted date: 02 Aug 2014

Published date: 11 Oct 2014

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

The pathophysiology underlying spinal cord injury is complex. Mechanistic understanding of the adaptive responses to injury is critical for targeted therapy aimed at reestablishing lost connections between proximal and distal neurons. After injury, cell-type specific gene transcription programs govern distinct cellular behaviors, and chromatin regulators play a central role in shaping the chromatin landscape to adjust transcriptional profiles in a context-dependent manner. In this review, we summarize recent progress on the pleiotropic roles of chromatin regulators in mediating the diverse adaptive behaviors of neurons and glial cells after spinal cord injury, and wherever possible, discuss the underlying mechanisms and genomic targets. We specifically draw attention to the perspective that takes into consideration the impact of epigenetic modulation on axon growth potential, together with its effect on wound-healing properties of glial cells. Epigenetic modulation of chromatin state represents an emerging therapeutic direction to promote neural repair and axon regeneration after spinal cord injury.

Cite this article

Jamie K. WONG , Hongyan ZOU . Reshaping the chromatin landscape after spinal cord injury[J]. Frontiers in Biology, 2014 , 9(5) : 356 -366 . DOI: 10.1007/s11515-014-1329-8

Acknowledgements

We apologize to colleagues whose work could not be cited owing to space limitations. H. Z. is supported by NIH (NS073596) and IrmaT. Hirschl/Monique Weill-Caulier Foundation.
1
Abematsu M, Tsujimura K, Yamano M, Saito M, Kohno K, Kohyama J, Namihira M, Komiya S, Nakashima K (2010). Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. J Clin Invest, 120(9): 3255–3266

DOI PMID

2
Aguzzi A, Barres B A, Bennett M L (2013). Microglia: scapegoat, saboteur, or something else? Science, 339(6116): 156–161

DOI PMID

3
Ashburner B P, Westerheide S D, Baldwin A S Jr (2001). The p65 (RelA) subunit of NF-κB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol Cell Biol, 21(20): 7065–7077

DOI PMID

4
Bardehle S, Krüger M, Buggenthin F, Schwausch J, Ninkovic J, Clevers H, Snippert H J, Theis F J, Meyer-Luehmann M, Bechmann I, Dimou L, Götz M (2013). Live imaging of astrocyte responses to acute injury reveals selective juxtavascular proliferation. Nat Neurosci, 16(5): 580–586

DOI PMID

5
Barnabé-Heider F, Göritz C, Sabelström H, Takebayashi H, Pfrieger F W, Meletis K, Frisén J (2010). Origin of new glial cells in intact and injured adult spinal cord. Cell Stem Cell, 7(4): 470–482

DOI PMID

6
Bartholdi D, Schwab M E (1997). Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: an in situ hybridization study. Eur J Neurosci, 9(7): 1422–1438

DOI PMID

7
Beck K D, Nguyen H X, Galvan M D, Salazar D L, Woodruff T M, Anderson A J (2010). Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain, 133(Pt 2): 433–447

DOI PMID

8
Bethea J R, Castro M, Keane R W, Lee T T, Dietrich W D, Yezierski R P (1998). Traumatic spinal cord injury induces nuclear factor-κB activation. J Neurosci, 18(9): 3251–3260

PMID

9
Broide R S, Redwine J M, Aftahi N, Young W, Bloom F E, Winrow C J (2007). Distribution of histone deacetylases 1-11 in the rat brain. J Mol Neurosci, 31(1): 47–58

DOI PMID

10
Buffo A, Rite I, Tripathi P, Lepier A, Colak D, Horn A P, Mori T, Götz M (2008). Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc Natl Acad Sci USA, 105(9): 3581–3586

DOI PMID

11
Carlson S L, Parrish M E, Springer J E, Doty K, Dossett L (1998). Acute inflammatory response in spinal cord following impact injury. Exp Neurol, 151(1): 77–88

DOI PMID

12
Carmel J B, Galante A, Soteropoulos P, Tolias P, Recce M, Young W, Hart R P (2001). Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss. Physiol Genomics, 7(2): 201–213

PMID

13
Chen L F, Fischle W, Verdin E, Greene W C (2001). Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science, 293(5535): 1653–1657

DOI PMID

14
Cho Y, Cavalli V (2012). HDAC5 is a novel injury-regulated tubulin deacetylase controlling axon regeneration. EMBO J, 31(14): 3063–3078

DOI PMID

15
Cho Y, Cavalli V (2014). HDAC signaling in neuronal development and axon regeneration. Curr Opin Neurobiol, 27C: 118–126

DOI PMID

16
Cho Y, Sloutsky R, Naegle K M, Cavalli V (2013). Injury-induced HDAC5 nuclear export is essential for axon regeneration. Cell, 155(4): 894–908

DOI PMID

17
David S, Kroner A (2011). Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci, 12(7): 388–399

DOI PMID

18
de Lima S, Koriyama Y, Kurimoto T, Oliveira J T, Yin Y, Li Y, Gilbert H Y, Fagiolini M, Martinez A M, Benowitz L (2012). Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc Natl Acad Sci USA, 109(23): 9149–9154

DOI PMID

19
De Santa F, Narang V, Yap Z H, Tusi B K, Burgold T, Austenaa L, Bucci G, Caganova M, Notarbartolo S, Casola S, Testa G, Sung W K, Wei C L, Natoli G (2009). Jmjd3 contributes to the control of gene expression in LPS-activated macrophages. EMBO J, 28(21): 3341–3352

DOI PMID

20
Elsharkawy A M, Oakley F, Lin F, Packham G, Mann D A, Mann J (2010). The NF-κB p50:p50:HDAC-1 repressor complex orchestrates transcriptional inhibition of multiple pro-inflammatory genes. J Hepatol, 53(3): 519–527

DOI PMID

21
Ernst J, Kheradpour P, Mikkelsen T S, Shoresh N, Ward L D, Epstein C B, Zhang X, Wang L, Issner R, Coyne M, Ku M, Durham T, Kellis M, Bernstein B E (2011). Mapping and analysis of chromatin state dynamics in nine human cell types. Nature, 473(7345): 43–49

DOI PMID

22
Faraco G, Pittelli M, Cavone L, Fossati S, Porcu M, Mascagni P, Fossati G, Moroni F, Chiarugi A (2009). Histone deacetylase (HDAC) inhibitors reduce the glial inflammatory response in vitro and in vivo. Neurobiol Dis, 36(2): 269–279

DOI PMID

23
Faulkner J R, Herrmann J E, Woo M J, Tansey K E, Doan N B, Sofroniew M V (2004). Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci, 24(9): 2143–2155

DOI PMID

24
Finelli M J, Wong J K, Zou H (2013). Epigenetic regulation of sensory axon regeneration after spinal cord injury. J Neurosci, 33(50): 19664–19676

DOI PMID

25
Gaub P, Joshi Y, Wuttke A, Naumann U, Schnichels S, Heiduschka P, Di Giovanni S (2011). The histone acetyltransferase p300 promotes intrinsic axonal regeneration. Brain, 134(Pt 7): 2134–2148

DOI PMID

26
Gaub P, Tedeschi A, Puttagunta R, Nguyen T, Schmandke A, 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(9): 1392–1408

DOI PMID

27
Gensel J C, Nakamura S, Guan Z, van Rooijen N, Ankeny D P, Popovich P G (2009). Macrophages promote axon regeneration with concurrent neurotoxicity. J Neurosci, 29(12): 3956–3968

DOI PMID

28
Gordon S, Martinez F O (2010). Alternative activation of macrophages: mechanism and functions. Immunity, 32(5): 593–604

DOI PMID

29
Göritz C, Dias D O, Tomilin N, Barbacid M, Shupliakov O, Frisén J (2011). A pericyte origin of spinal cord scar tissue. Science, 333(6039): 238–242

DOI PMID

30
Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G (2014). In Vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model. Cell Stem Cell, 14(2): 188–202

DOI PMID

31
Hsieh J, Nakashima K, Kuwabara T, Mejia E, Gage F H (2004). Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc Natl Acad Sci USA, 101(47): 16659–16664

DOI PMID

32
Ishii K, Toda M, Nakai Y, Asou H, Watanabe M, Nakamura M, Yato Y, Fujimura Y, Kawakami Y, Toyama Y, Uyemura K (2001). Increase of oligodendrocyte progenitor cells after spinal cord injury. J Neurosci Res, 65(6): 500–507

DOI PMID

33
Iskandar B J, Rizk E, Meier B, Hariharan N, Bottiglieri T, Finnell R H, Jarrard D F, Banerjee R V, Skene J H, Nelson A, Patel N, Gherasim C, Simon K, Cook T D, Hogan K J (2010). Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation. J Clin Invest, 120(5): 1603–1616

DOI PMID

34
Karow M, Sánchez R, Schichor C, Masserdotti G, Ortega F, Heinrich C, Gascón S, Khan M A, Lie D C, Dellavalle A, Cossu G, Goldbrunner R, Götz M, Berninger B (2012). Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells. Cell Stem Cell, 11(4): 471–476

DOI PMID

35
Kigerl K A, Gensel J C, Ankeny D P, Alexander J K, Donnelly D J, Popovich P G (2009). Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci, 29(43): 13435–13444

DOI PMID

36
Kim J Y, Shen S, Dietz K, He Y, Howell O, Reynolds R, Casaccia P (2010). HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage. Nat Neurosci, 13(2): 180–189

DOI PMID

37
Konsoula Z, Barile F A (2012). Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders. J Pharmacol Toxicol Methods, 66(3): 215–220

DOI PMID

38
Kouzarides T (2007). Chromatin modifications and their function. Cell, 128(4): 693–705

DOI PMID

39
Lee J Y, Kim H S, Choi H Y, Oh T H, Ju B G, Yune T Y (2012). Valproic acid attenuates blood-spinal cord barrier disruption by inhibiting matrix metalloprotease-9 activity and improves functional recovery after spinal cord injury. J Neurochem, 121(5): 818–829

DOI PMID

40
Lindner R, Puttagunta R, Di Giovanni S (2013). Epigenetic regulation of axon outgrowth and regeneration in CNS injury: the first steps forward. Neurotherapeutics, 10(4): 771–781

DOI PMID

41
Liu H, Hu Q, D’ercole A J, Ye P (2009). Histone deacetylase 11 regulates oligodendrocyte-specific gene expression and cell development in OL-1 oligodendroglia cells. Glia, 57(1): 1–12

DOI PMID

42
Liu K, Tedeschi A, Park K K, He Z (2011). Neuronal intrinsic mechanisms of axon regeneration. Annu Rev Neurosci, 34(1): 131–152

DOI PMID

43
Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig E S, Havton L A, Zheng B, Conner J M, Marsala M, Tuszynski M H (2012). Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell, 150(6): 1264–1273

DOI PMID

44
Lu W H, Wang C Y, Chen P S, Wang J W, Chuang D M, Yang C S, Tzeng S F (2013). Valproic acid attenuates microgliosis in injured spinal cord and purinergic P2X4 receptor expression in activated microglia. J Neurosci Res, 91(5): 694–705

DOI PMID

45
Lv L, Han X, Sun Y, Wang X, Dong Q (2012). Valproic acid improves locomotion in vivo after SCI and axonal growth of neurons in vitro. Exp Neurol, 233(2): 783–790

DOI PMID

46
Lv L, Sun Y, Han X, Xu C C, Tang Y P, Dong Q (2011). Valproic acid improves outcome after rodent spinal cord injury: potential roles of histone deacetylase inhibition. Brain Res, 1396: 60–68

DOI PMID

47
McTigue D M, Wei P, Stokes B T (2001). Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J Neurosci, 21(10): 3392–3400

PMID

48
Montgomery R L, Hsieh J, Barbosa A C, Richardson J A, Olson E N (2009). Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development. Proc Natl Acad Sci USA, 106(19): 7876–7881

DOI PMID

49
Monti B, Polazzi E, Contestabile A (2009). Biochemical, molecular and epigenetic mechanisms of valproic acid neuroprotection. Curr Mol Pharmacol2: 95–109

50
Mullican S E, Gaddis C A, Alenghat T, Nair M G, Giacomin P R, Everett L J, Feng D, Steger D J, Schug J, Artis D, Lazar M A (2011). Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev, 25(23): 2480–2488

DOI PMID

51
Neumann S, Woolf C J (1999). Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron, 23(1): 83–91

DOI PMID

52
Niu W, Zang T, Zou Y, Fang S, Smith D K, Bachoo R, Zhang C L (2013). In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat Cell Biol, 15(10): 1164–1175

DOI PMID

53
Oakley F, Mann J, Nailard S, Smart D E, Mungalsingh N, Constandinou C, Ali S, Wilson S J, Millward-Sadler H, Iredale J P, Mann D A (2005). Nuclear factor-κB1 (p50) limits the inflammatory and fibrogenic responses to chronic injury. Am J Pathol, 166(3): 695–708

DOI PMID

54
Parikh P, Hao Y, Hosseinkhani M, Patil S B, Huntley G W, Tessier-Lavigne M, Zou H (2011). Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons. Proc Natl Acad Sci USA, 108(19): E99–E107

DOI PMID

55
Peleg S (2010). Memory impairment in mice altered histone acetylation is associated with age-dependent. Science, 328: 753–756

DOI PMID

56
Ponomarev E D, Maresz K, Tan Y, Dittel B N (2007). CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells. J Neurosci, 27(40): 10714–10721

DOI PMID

57
Popovich P G, Jones T B (2003). Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics. Trends Pharmacol Sci, 24(1): 13–17

DOI PMID

83
Popovich P G, Longbrake E E (2008). Can the immune system be harnessed to repair the CNS?Nat Rev Neurosci, 9: 481–493

58
Puttagunta R, Tedeschi A, Sória M G, Hervera A, Lindner R, Rathore K I, Gaub P, Joshi Y, Nguyen T, Schmandke A, Laskowski C J, Boutillier A L, Bradke F, Di Giovanni S (2014). PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system. Nat Commun, 5: 3527

DOI PMID

59
Ram O, Goren A, Amit I, Shoresh N, Yosef N, Ernst J, Kellis M, Gymrek M, Issner R, Coyne M, Durham T, Zhang X, Donaghey J, Epstein C B, Regev A, Bernstein B E (2011). Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells. Cell, 147(7): 1628–1639

DOI PMID

60
Richardson P M, Issa V M (1984). Peripheral injury enhances central regeneration of primary sensory neurones. Nature, 309(5971): 791–793

DOI PMID

61
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, Ratan R R, Langley B (2009). HDAC6 is a target for protection and regeneration following injury in the nervous system. Proc Natl Acad Sci USA, 106(46): 19599–19604

DOI PMID

62
Sabelström H, Stenudd M, Réu P, Dias D O, Elfineh M, Zdunek S, Damberg P, Göritz C, Frisén J (2013). Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice. Science, 342(6158): 637–640

DOI PMID

63
Shen S, Sandoval J, Swiss V A, Li J, Dupree J, Franklin R J, Casaccia-Bonnefil P (2008). Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nat Neurosci, 11(9): 1024–1034

DOI PMID

64
Silver J, Miller J H (2004). Regeneration beyond the glial scar. Nat Rev Neurosci, 5(2): 146–156

DOI PMID

65
Stolt C C, Rehberg S, Ader M, Lommes P, Riethmacher D, Schachner M, Bartsch U, Wegner M (2002). Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10. Genes Dev, 16(2): 165–170

DOI PMID

66
Su Z, Niu W, Liu M L, Zou Y, Zhang C L (2014). In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat Commun, 5: 3338

DOI PMID

67
Su Z, Yuan Y, Chen J, Zhu Y, Qiu Y, Zhu F, Huang A, He C (2011). Reactive astrocytes inhibit the survival and differentiation of oligodendrocyte precursor cells by secreted TNF-α. J Neurotrauma, 28(6): 1089–1100

DOI PMID

68
Suyama K, Watanabe M, Sakai D, Osada T, Imai M, Mochida J (2007). Nkx2.2 expression in differentiation of oligodendrocyte precursor cells and inhibitory factors for differentiation of oligodendrocytes after traumatic spinal cord injury. J Neurotrauma, 24(6): 1013–1025

DOI PMID

69
Tang B L (2014). Class II HDACs and neuronal regeneration. J Cell Biochem, 115(7): 1225–1233

DOI PMID

70
Tedeschi A, Nguyen T, Puttagunta R, Gaub P, Di Giovanni S (2009). A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration. Cell Death Differ, 16(4): 543–554

DOI PMID

71
Torper O, Pfisterer U, Wolf D A, Pereira M, Lau S, Jakobsson J, Björklund A, Grealish S, Parmar M (2013). Generation of induced neurons via direct conversion in vivo. Proc Natl Acad Sci USA, 110(17): 7038–7043

DOI PMID

72
Totoiu M O, Keirstead H S (2005). Spinal cord injury is accompanied by chronic progressive demyelination. J Comp Neurol, 486(4): 373–383

DOI PMID

73
Trakhtenberg E F, Goldberg J L (2012). Epigenetic regulation of axon and dendrite growth. Front Mol Neurosci, 5: 24

DOI PMID

74
Wang Y, Cheng X, He Q, Zheng Y, Kim D H, Whittemore S R, Cao Q L (2011). Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins. J Neurosci, 31(16): 6053–6058

DOI PMID

75
Wanner I B, Anderson M A, Song B, Levine J, Fernandez A, Gray-Thompson Z, Ao Y, Sofroniew M V (2013). Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci, 33(31): 12870–12886

DOI PMID

76
Wisniewski H M, Bloom B R (1975). Primary demyelination as a nonspecific consequence of a cell-mediated immune reaction. J Exp Med, 141(2): 346–359

DOI PMID

77
Xu J, Fan G, Chen S, Wu Y, Xu X M, Hsu C Y (1998). Methylprednisolone inhibition of TNF-α expression and NF-κB activation after spinal cord injury in rats. Brain Res Mol Brain Res, 59(2): 135–142

DOI PMID

78
Ye F, Chen Y, Hoang T, Montgomery R L, Zhao X H, Bu H, Hu T, Taketo M M, van Es J H, Clevers H, Hsieh J, Bassel-Duby R, Olson E N, Lu Q R (2009). HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the β-catenin-TCF interaction. Nat Neurosci, 12(7): 829–838

DOI PMID

79
York E M, Petit A, Roskams A J (2013). Epigenetics of neural repair following spinal cord injury. Neurotherapeutics, 10(4): 757–770

DOI PMID

80
Zamanian J L, Xu L, Foo L C, Nouri N, Zhou L, Giffard R G, Barres B A (2012). Genomic analysis of reactive astrogliosis. J Neurosci, 32(18): 6391–6410

DOI PMID

81
Zhong J, Zou H (2014). BMP signaling in axon regeneration. Curr Opin Neurobiol, 27C: 127–134

DOI PMID

82
Zou H, Ho C, Wong K, Tessier-Lavigne M (2009). Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons. J Neurosci, 29(22): 7116–7123

DOI PMID

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