Neuronal Genome Plasticity: Retrotransposons, Environment and Disease



The neuronal genome has long been considered as a stably persisting entity interpreted as the foundation of neurobiology. Over the past decade, it has become increasingly clear that mobile genetic elements, such as the retrotransposon LINE-1 (L1), are actively transcribed and transpose in the healthy brain. L1 activity therefore provides a route to somatic genome diversity and dynamism in neuronal populations. Here, we discuss the discovery of L1 retrotransposition during neurogenesis, and consider how neuronal cells regulate retrotransposition in response to endogenous and environmental stimuli. We also bring forward hypotheses relating to how L1 impacts normal brain development and function, as well as how abnormal L1 mobilisation could contribute to neurological disease susceptibility and pathophysiology.


Retrotransposon LINE-1 Neuron Neurogenesis Mosaicism 


  1. Akindipe T, Wilson D, Stein DJ (2014) Psychiatric disorders in individuals with methamphetamine dependence: prevalence and risk factors. Metab Brain Dis 29(2):351–357PubMedCrossRefGoogle Scholar
  2. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, ArlingtonCrossRefGoogle Scholar
  3. Amir RE et al (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23(2):185–188PubMedCrossRefGoogle Scholar
  4. Athanikar JN, Badge RM, Moran JV (2004) A YY1-binding site is required for accurate human LINE-1 transcription initiation. Nucleic Acids Res 32(13):3846–3855PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bagot RC et al (2014) Epigenetic signaling in psychiatric disorders: stress and depression. Dialogues Clin Neurosci 16(3):281–295PubMedPubMedCentralGoogle Scholar
  6. Baillie JK et al (2011) Somatic retrotransposition alters the genetic landscape of the human brain. Nature 479(7374):534–537PubMedPubMedCentralCrossRefGoogle Scholar
  7. Beck CR et al (2010) LINE-1 retrotransposition activity in human genomes. Cell 141(7):1159–1170PubMedPubMedCentralCrossRefGoogle Scholar
  8. Beck CR et al (2011) LINE-1 elements in structural variation and disease. Annu Rev Genomics Hum Genet 12:187–215PubMedPubMedCentralCrossRefGoogle Scholar
  9. Becker CM (1990) Disorders of the inhibitory glycine receptor: the spastic mouse. FASEB J 4(10):2767–2774PubMedGoogle Scholar
  10. Becker KG et al (1993) Binding of the ubiquitous nuclear transcription factor YY1 to a cis regulatory sequence in the human LINE-1 transposable element. Hum Mol Genet 2(10):1697–1702PubMedCrossRefGoogle Scholar
  11. Bejerano G et al (2006) A distal enhancer and an ultraconserved exon are derived from a novel retroposon. Nature 441(7089):87–90PubMedCrossRefGoogle Scholar
  12. Belancio VP et al (2010) Somatic expression of LINE-1 elements in human tissues. Nucleic Acids Res 38(12):3909–3922PubMedPubMedCentralCrossRefGoogle Scholar
  13. Berger A et al (2014) Direct binding of the Alu binding protein dimer SRP9/14 to 40S ribosomal subunits promotes stress granule formation and is regulated by Alu RNA. Nucleic Acids Res 42(17):11203–11217PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bergsland M et al (2006) The establishment of neuronal properties is controlled by Sox4 and Sox11. Genes Dev 20(24):3475–3486PubMedPubMedCentralCrossRefGoogle Scholar
  15. Böhne A et al (2008) Transposable elements as drivers of genomic and biological diversity in vertebrates. Chromosome Res 16(1):203–215PubMedCrossRefGoogle Scholar
  16. Bollati V et al (2011) DNA methylation in repetitive elements and Alzheimer disease. Brain Behav Immun 25(6):1078–1083PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bourque G (2009) Transposable elements in gene regulation and in the evolution of vertebrate genomes. Curr Opin Genet Dev 19(6):607–612PubMedCrossRefGoogle Scholar
  18. Brouha B et al (2003) Hot L1s account for the bulk of retrotransposition in the human population. Proc Natl Acad Sci U S A 100(9):5280–5285PubMedPubMedCentralCrossRefGoogle Scholar
  19. Brown AS (2011) The environment and susceptibility to schizophrenia. Prog Neurobiol 93(1):23–58PubMedCrossRefGoogle Scholar
  20. Bundo M et al (2014) Increased L1 retrotransposition in the neuronal genome in schizophrenia. Neuron 81(2):306–313PubMedCrossRefGoogle Scholar
  21. Casacuberta E, González J (2013) The impact of transposable elements in environmental adaptation. Mol Ecol 22(6):1503–1517PubMedCrossRefGoogle Scholar
  22. Chen J, Rattner A, Nathans J (2006) Effects of L1 retrotransposon insertion on transcript processing, localization and accumulation: lessons from the retinal degeneration 7 mouse and implications for the genomic ecology of L1 elements. Hum Mol Genet 15(13):2146–2156PubMedCrossRefGoogle Scholar
  23. Coufal NG et al (2009) L1 retrotransposition in human neural progenitor cells. Nature 460(7259):1127–1131PubMedPubMedCentralCrossRefGoogle Scholar
  24. Coufal NG et al (2011) Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells. Proc Natl Acad Sci U S A 108(51):20382–20387PubMedPubMedCentralCrossRefGoogle Scholar
  25. D’Arcangelo G et al (1995) A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374(6524):719–723PubMedCrossRefGoogle Scholar
  26. de Bergeyck V et al (1997) A truncated Reelin protein is produced but not secreted in the “Orleans” reeler mutation (Relnrl-Orl). Mol Brain Res 50(1–2):85–90PubMedCrossRefGoogle Scholar
  27. Denli AM et al (2015) Primate-specific ORF0 contributes to retrotransposon-mediated diversity. Cell 163(3):583–593PubMedCrossRefGoogle Scholar
  28. Dewannieux M, Esnault C, Heidmann T (2003) LINE-mediated retrotransposition of marked Alu sequences. Nat Genet 35(1):41–48PubMedCrossRefGoogle Scholar
  29. Doucet AJ et al (2015) A 3′ Poly(A) tract is required for LINE-1 retrotransposition. Mol Cell 60(5):728–741PubMedPubMedCentralCrossRefGoogle Scholar
  30. El-Sawy M et al (2005) Nickel stimulates L1 retrotransposition by a post-transcriptional mechanism. J Mol Biol 354(2):246–257PubMedPubMedCentralCrossRefGoogle Scholar
  31. Eriksson PS et al (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317PubMedCrossRefGoogle Scholar
  32. Evrony GD et al (2012) Single-neuron sequencing analysis of L1 retrotransposition and somatic mutation in the human brain. Cell 151(3):483–496PubMedPubMedCentralCrossRefGoogle Scholar
  33. Ewing AD, Kazazian HH (2011) Whole-genome resequencing allows detection of many rare LINE-1 insertion alleles in humans. Genome Res 21(6):985–990PubMedPubMedCentralCrossRefGoogle Scholar
  34. Farkash EA et al (2006) Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay. Nucleic Acids Res 34(4):1196–1204PubMedPubMedCentralCrossRefGoogle Scholar
  35. Farzan F et al (2010) Evidence for gamma inhibition deficits in the dorsolateral prefrontal cortex of patients with schizophrenia. Brain 133(Pt 5):1505–1514PubMedCrossRefGoogle Scholar
  36. Faulkner GJ et al (2009) The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41(5):563–571PubMedCrossRefGoogle Scholar
  37. Feschotte C (2008) Transposable elements and the evolution of regulatory networks. Nat Rev Genet 9(5):397–405PubMedPubMedCentralCrossRefGoogle Scholar
  38. Fort A et al (2014) Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nat Genet 46(6):558–566PubMedCrossRefGoogle Scholar
  39. Fuks F et al (2003) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 278(6):4035–4040PubMedCrossRefGoogle Scholar
  40. Gabel HW et al (2015) Disruption of DNA-methylation-dependent long gene repression in Rett syndrome. Nature 522(7554):89–93PubMedPubMedCentralCrossRefGoogle Scholar
  41. Garcia-Perez JL et al (2007a) Distinct mechanisms for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase. Genome Res 17(5):602–611PubMedPubMedCentralCrossRefGoogle Scholar
  42. Garcia-Perez JL et al (2007b) LINE-1 retrotransposition in human embryonic stem cells. Hum Mol Genet 16(13):1569–1577PubMedCrossRefGoogle Scholar
  43. Garcia-Perez JL et al (2010) Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells. Nature 466(7307):769–773PubMedPubMedCentralCrossRefGoogle Scholar
  44. Gifford WD, Pfaff SL, Macfarlan TS (2013) Transposable elements as genetic regulatory substrates in early development. Trends Cell Biol 23(5):218–226PubMedPubMedCentralCrossRefGoogle Scholar
  45. Giorgi G, Marcantonio P, Del Re B (2011) LINE-1 retrotransposition in human neuroblastoma cells is affected by oxidative stress. Cell Tissue Res 346(3):383–391PubMedCrossRefGoogle Scholar
  46. Graham V et al (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39(5):749–765PubMedCrossRefGoogle Scholar
  47. Grimaldi G, Skowronski J, Singer M (1984) Defining the beginning and end of KpnI family segments. EMBO J 3(8):1753–1759PubMedPubMedCentralGoogle Scholar
  48. Guillozet-Bongaarts AL et al (2014) Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 19(4):478–485PubMedCrossRefGoogle Scholar
  49. Guy J et al (2007) Reversal of neurological defects in a mouse model of Rett syndrome. Science 315(5815):1143–1147PubMedCrossRefGoogle Scholar
  50. Habibi L et al (2014) Mercury specifically induces LINE-1 activity in a human neuroblastoma cell line. Mutat Res 759:9–20CrossRefGoogle Scholar
  51. Han JS, Boeke JD (2004) A highly active synthetic mammalian retrotransposon. Nature 429(6989):314–318PubMedCrossRefGoogle Scholar
  52. Han JS, Szak ST, Boeke JD (2004) Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes. Nature 429(6989):268–274PubMedCrossRefGoogle Scholar
  53. Haoudi A et al (2004) Retrotransposition-competent human LINE-1 induces apoptosis in cancer cells with intact p53. J Biomed Biotechnol 2004(4):185–194PubMedPubMedCentralCrossRefGoogle Scholar
  54. Harris CR et al (2009) p53 responsive elements in human retrotransposons. Oncogene 28(44):3857–3865PubMedPubMedCentralCrossRefGoogle Scholar
  55. Haslinger A et al (2009) Expression of Sox11 in adult neurogenic niches suggests a stage-specific role in adult neurogenesis. Eur J Neurosci 29(11):2103–2114PubMedCrossRefGoogle Scholar
  56. Hata K, Sakaki Y (1997) Identification of critical CpG sites for repression of L1 transcription by DNA methylation. Gene 189(2):227–234PubMedCrossRefGoogle Scholar
  57. He Y, Casaccia-Bonnefil P (2008) The Yin and Yang of YY1 in the nervous system. J Neurochem 106(4):1493–1502PubMedPubMedCentralCrossRefGoogle Scholar
  58. Heinrich C et al (2014) Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Reports 3(6):1000–1014PubMedPubMedCentralCrossRefGoogle Scholar
  59. Hutchins AP, Pei D (2015) Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming, and long non-coding RNAs. Sci Bull (Beijing) 60(20):1722–1733CrossRefGoogle Scholar
  60. Inoue K, Shiga T, Ito Y (2008) Runx transcription factors in neuronal development. Neural Dev 3(1):20PubMedPubMedCentralCrossRefGoogle Scholar
  61. Iskow RC et al (2010) Natural mutagenesis of human genomes by endogenous retrotransposons. Cell 141(7):1253–1261PubMedPubMedCentralCrossRefGoogle Scholar
  62. Jacobsen LK, Southwick SM, Kosten TR (2001) Substance use disorders in patients with posttraumatic stress disorder: a review of the literature. Am J Psychiatry 158(8):1184–1190PubMedCrossRefGoogle Scholar
  63. Jacques P-É, Jeyakani J, Bourque G (2013) The majority of primate-specific regulatory sequences are derived from transposable elements. PLoS Genet 9(5):e1003504PubMedPubMedCentralCrossRefGoogle Scholar
  64. Johnson R, Guigo R (2014) The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs. RNA 20(7):959–976PubMedPubMedCentralCrossRefGoogle Scholar
  65. Jordan IK et al (2003) Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet 19(2):68–72PubMedCrossRefGoogle Scholar
  66. Joshi D, Fullerton JM, Weickert CS (2014) Elevated ErbB4 mRNA is related to interneuron deficit in prefrontal cortex in schizophrenia. J Psychiatr Res 53:125–132PubMedCrossRefGoogle Scholar
  67. Kale SP et al (2005) Heavy metals stimulate human LINE-1 retrotransposition. Int J Environ Res Public Health 2(1):14–23PubMedPubMedCentralCrossRefGoogle Scholar
  68. Kale SP et al (2006) The L1 retrotranspositional stimulation by particulate and soluble cadmium exposure is independent of the generation of DNA breaks. Int J Environ Res Public Health 3(2):121–128PubMedPubMedCentralCrossRefGoogle Scholar
  69. Kano H et al (2009) L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism. Genes Dev 23(11):1303–1312PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kazazian HH et al (1988) Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature 332(6160):164–166PubMedCrossRefGoogle Scholar
  71. Kelley DR et al (2014) Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions. Genome Biol 15(12):537PubMedPubMedCentralCrossRefGoogle Scholar
  72. Kim S et al (2015) Memory, scene construction, and the human hippocampus. Proc Natl Acad Sci U S A 112(15):4767–4772PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kimoto S, Bazmi HH, Lewis DA (2014) Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in schizophrenia: contribution of altered regulation by Zif268. Am J Psychiatry 171(9):969–978PubMedPubMedCentralCrossRefGoogle Scholar
  74. Kingsmore SF et al (1994) Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet 7(2):136–141PubMedCrossRefGoogle Scholar
  75. Klawitter S et al (2016) Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells. Nat Commun 7:10286PubMedPubMedCentralCrossRefGoogle Scholar
  76. Koehl M (2015) Gene-environment interaction in programming hippocampal plasticity: focus on adult neurogenesis. Front Mol Neurosci 8:41PubMedPubMedCentralCrossRefGoogle Scholar
  77. Kurnosov AA et al (2015) The evidence for increased L1 activity in the site of human adult brain neurogenesis. PLoS One 10(2):e0117854PubMedPubMedCentralCrossRefGoogle Scholar
  78. Kuwabara T et al (2009) Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci 12(9):1097–1105PubMedPubMedCentralCrossRefGoogle Scholar
  79. Kwapis JL, Wood MA (2014) Epigenetic mechanisms in fear conditioning: implications for treating post-traumatic stress disorder. Trends Neurosci 37(12):706–720PubMedPubMedCentralCrossRefGoogle Scholar
  80. Lallemend F et al (2012) Positional differences of axon growth rates between sensory neurons encoded by Runx3. EMBO J 31(18):3718–3729PubMedPubMedCentralCrossRefGoogle Scholar
  81. Lander E et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921PubMedCrossRefGoogle Scholar
  82. Lennartsson A et al (2015) Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors. Epigenetics Chromatin 8(1):55PubMedPubMedCentralCrossRefGoogle Scholar
  83. Li T-H, Schmid CW (2001) Differential stress induction of individual Alu loci: implications for transcription and retrotransposition. Gene 276(1–2):135–141PubMedCrossRefGoogle Scholar
  84. Li W et al (2012) Transposable elements in TDP-43-mediated neurodegenerative disorders. PLoS One 7(9):e44099PubMedPubMedCentralCrossRefGoogle Scholar
  85. Li W et al (2013) Activation of transposable elements during aging and neuronal decline in Drosophila. Nat Neurosci 16(5):529–531PubMedPubMedCentralCrossRefGoogle Scholar
  86. Maze I et al (2011) Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens. Proc Natl Acad Sci U S A 108(7):3035–3040PubMedPubMedCentralCrossRefGoogle Scholar
  87. McClintock B (1950) The origin and behavior of mutable loci in maize. Proc Natl Acad Sci U S A 36(6):344–355PubMedPubMedCentralCrossRefGoogle Scholar
  88. McClintock B (1984) The significance of responses of the genome to challenge. Science 226(4676):792–801PubMedCrossRefGoogle Scholar
  89. McDonald RJ, Hong NS (2013) How does a specific learning and memory system in the mammalian brain gain control of behavior? Hippocampus 23(11):1084–1102PubMedCrossRefGoogle Scholar
  90. Miki Y et al (1992) Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res 52(3):643–645PubMedGoogle Scholar
  91. Mir AA, Philippe C, Cristofari G (2015) euL1db: the European database of L1HS retrotransposon insertions in humans. Nucleic Acids Res 43(Database issue):D43–D47PubMedCrossRefGoogle Scholar
  92. Modabbernia A, Arora M, Reichenberg A (2016) Environmental exposure to metals, neurodevelopment, and psychosis. Curr Opin Pediatr 28(2):243–249PubMedCrossRefGoogle Scholar
  93. Moran JV et al (1996) High frequency retrotransposition in cultured mammalian cells. Cell 87(5):917–927PubMedCrossRefGoogle Scholar
  94. Morrish TA et al (2002) DNA repair mediated by endonuclease-independent LINE-1 retrotransposition. Nat Genet 31(2):159–165PubMedCrossRefGoogle Scholar
  95. Mu L et al (2012) SoxC transcription factors Are required for neuronal differentiation in adult hippocampal neurogenesis. J Neurosci 32(9):3067–3080PubMedPubMedCentralCrossRefGoogle Scholar
  96. Mülhardt C et al (1994) The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron 13(4):1003–1015PubMedCrossRefGoogle Scholar
  97. Muotri AR et al (2005) Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition. Nature 435(7044):903–910PubMedCrossRefGoogle Scholar
  98. Muotri AR et al (2009) Environmental influence on L1 retrotransposons in the adult hippocampus. Hippocampus 19(10):1002–1007PubMedPubMedCentralCrossRefGoogle Scholar
  99. Muotri AR et al (2010) L1 retrotransposition in neurons is modulated by MeCP2. Nature 468(7322):443–446PubMedPubMedCentralCrossRefGoogle Scholar
  100. Nan X et al (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393(6683):386–389PubMedCrossRefGoogle Scholar
  101. Okudaira N, Ishizaka Y, Nishio H (2014) Retrotransposition of long interspersed element 1 induced by methamphetamine or cocaine. J Biol Chem 289(37):25476–25485PubMedPubMedCentralCrossRefGoogle Scholar
  102. Oliver KR, Greene WK (2011) Mobile DNA and the TE-Thrust hypothesis: supporting evidence from the primates. Mob DNA 2(1):8PubMedPubMedCentralCrossRefGoogle Scholar
  103. Ostertag EM (2000) Determination of L1 retrotransposition kinetics in cultured cells. Nucleic Acids Res 28(6):1418–1423PubMedPubMedCentralCrossRefGoogle Scholar
  104. Pandey R et al (2011) Heat shock factor binding in Alu repeats expands its involvement in stress through an antisense mechanism. Genome Biol 12(11):R117PubMedPubMedCentralCrossRefGoogle Scholar
  105. Peaston AE et al (2004) Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell 7(4):597–606PubMedCrossRefGoogle Scholar
  106. Reilly MT et al (2013) The role of transposable elements in health and diseases of the central nervous system. J Neurosci 33(45):17577–17586PubMedPubMedCentralCrossRefGoogle Scholar
  107. Richardson SR, Morell S, Faulkner GJ (2014) L1 retrotransposons and somatic mosaicism in the brain. Annu Rev Genet 48:1–27PubMedCrossRefGoogle Scholar
  108. Ring KL et al (2012) Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor. Cell Stem Cell 11(1):100–109PubMedPubMedCentralCrossRefGoogle Scholar
  109. Rusiecki JA et al (2012) DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members. Epigenomics 4(1):29–40PubMedCrossRefGoogle Scholar
  110. Rylski M et al (2008) Yin Yang 1 expression in the adult rodent brain. Neurochem Res 33(12):2556–2564PubMedCrossRefGoogle Scholar
  111. Sasaki T et al (2008) Possible involvement of SINEs in mammalian-specific brain formation. Proc Natl Acad Sci U S A 105(11):4220–4225PubMedPubMedCentralCrossRefGoogle Scholar
  112. Sassaman DM et al (1997) Many human L1 elements are capable of retrotransposition. Nat Genet 16(1):37–43PubMedCrossRefGoogle Scholar
  113. Scott AF et al (1987) Origin of the human L1 elements: proposed progenitor genes deduced from a consensus DNA sequence. Genomics 1(2):113–125PubMedCrossRefGoogle Scholar
  114. Segman RH et al (2005) Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Mol Psychiatry 10(5):500–513, 425PubMedCrossRefGoogle Scholar
  115. Shahbazian MD (2002) Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 11(2):115–124PubMedCrossRefGoogle Scholar
  116. Shiloh Y (2001) ATM (ataxia telangiectasia mutated): expanding roles in the DNA damage response and cellular homeostasis. Biochem Soc Trans 29(6):661–666PubMedCrossRefGoogle Scholar
  117. Shukla R et al (2013) Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell 153(1):101–111PubMedPubMedCentralCrossRefGoogle Scholar
  118. Singer MF et al (1993) LINE-1: a human transposable element. Gene 135(1–2):183–188PubMedCrossRefGoogle Scholar
  119. Singer T et al (2010) LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes? Trends Neurosci 33(8):345–354PubMedPubMedCentralCrossRefGoogle Scholar
  120. Spadafora C (2015) A LINE-1-encoded reverse transcriptase-dependent regulatory mechanism is active in embryogenesis and tumorigenesis. Ann N Y Acad Sci 1341:164–171PubMedCrossRefGoogle Scholar
  121. Stribinskis V, Ramos KS (2006) Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen. Cancer Res 66(5):2616–2620PubMedCrossRefGoogle Scholar
  122. Symer DE et al (2002) Human L1 retrotransposition is associated with genetic instability in vivo. Cell 110:327–338PubMedCrossRefGoogle Scholar
  123. Takahara T et al (1996) Dysfunction of the Orleans reeler gene arising from exon skipping due to transposition of a full-length copy of an active L1 sequence into the skipped exon. Hum Mol Genet 5(7):989–993PubMedCrossRefGoogle Scholar
  124. Taylor AMR et al (2015) Ataxia telangiectasia: more variation at clinical and cellular levels. Clin Genet 87(3):199–208PubMedCrossRefGoogle Scholar
  125. Tchénio T, Casella JF, Heidmann T (2000) Members of the SRY family regulate the human LINE retrotransposons. Nucleic Acids Res 28(2):411–415PubMedPubMedCentralCrossRefGoogle Scholar
  126. Tedeschi A, Di Giovanni S (2009) The non-apoptotic role of p53 in neuronal biology: enlightening the dark side of the moon. EMBO Rep 10(6):576–583PubMedPubMedCentralCrossRefGoogle Scholar
  127. Teng SC, Kim B, Gabriel A (1996) Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaks. Nature 383(6601):641–644PubMedCrossRefGoogle Scholar
  128. Tipps ME, Raybuck JD, Lattal KM (2014) Substance abuse, memory, and post-traumatic stress disorder. Neurobiol Learn Mem 112:87–100PubMedCrossRefGoogle Scholar
  129. Trelogan SA, Martin SL (1995) Tightly regulated, developmentally specific expression of the first open reading frame from LINE-1 during mouse embryogenesis. Proc Natl Acad Sci 92(5):1520–1524PubMedPubMedCentralCrossRefGoogle Scholar
  130. Tyekucheva S et al (2011) Establishing the baseline level of repetitive element expression in the human cortex. BMC Genomics 12:495PubMedPubMedCentralCrossRefGoogle Scholar
  131. Upton KR et al (2015) Ubiquitous L1 mosaicism in hippocampal neurons. Cell 161(2):228–239PubMedPubMedCentralCrossRefGoogle Scholar
  132. Van Meter M et al (2014) SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun 5:5011PubMedPubMedCentralCrossRefGoogle Scholar
  133. Wallace NA, Belancio VP, Deininger PL (2008) L1 mobile element expression causes multiple types of toxicity. Gene 419(1–2):75–81PubMedPubMedCentralCrossRefGoogle Scholar
  134. Wei W et al (2001) Human L1 retrotransposition: cis preference versus trans complementation. Mol Cell Biol 21(4):1429–1439PubMedPubMedCentralCrossRefGoogle Scholar
  135. Weïwer M et al (2013) Therapeutic potential of isoform selective HDAC inhibitors for the treatment of schizophrenia. Future Med Chem 5(13):1491–1508PubMedCrossRefGoogle Scholar
  136. Wright AV, Nuñez JK, Doudna JA (2016) Biology and applications of CRISPR systems: harnessing nature’s toolbox for genome engineering. Cell 164(1–2):29–44PubMedCrossRefGoogle Scholar
  137. Wylie A et al (2015) p53 genes function to restrain mobile elements. Genes Dev 30(1):64–77PubMedCrossRefGoogle Scholar
  138. Yang N et al (2003) An important role for RUNX3 in human L1 transcription and retrotransposition. Nucleic Acids Res 31(16):4929–4940PubMedPubMedCentralCrossRefGoogle Scholar
  139. Yu F et al (2001) Methyl-CpG-binding protein 2 represses LINE-1 expression and retrotransposition but not Alu transcription. Nucleic Acids Res 29(21):4493–4501PubMedPubMedCentralCrossRefGoogle Scholar
  140. Zhornitsky S et al (2015) Psychopathology in substance use disorder patients with and without substance-induced psychosis. J Addict 2015:843762PubMedPubMedCentralGoogle Scholar
  141. Zovkic IB, Sweatt JD (2013) Epigenetic mechanisms in learned fear: implications for PTSD. Neuropsychopharmacology 38(1):77–93PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Mater Research Institute, University of QueenslandBrisbaneAustralia
  2. 2.Queensland Brain Institute, University of QueenslandBrisbaneAustralia

Personalised recommendations