Reactivation of Endogenous Retroelements in Cancer Development and Therapy

Literature Cited

1. Adoue V, Binet B, Malbec A, Fourquet J, Romagnoli P et al. 2019. The histone methyltransferase SETDB1 controls T helper cell lineage integrity by repressing endogenous retroviruses. Immunity 50:629–44.e8
   [Google Scholar]
2. Aguilera A, García-Muse T. 2012. R loops: from transcription byproducts to threats to genome stability. Mol. Cell 46:115–24
   [Google Scholar]
3. Ahmad S, Mu X, Yang F, Greenwald E, Park JW et al. 2018. Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation. Cell 172:797–810.e13
   [Google Scholar]
4. Allis CD, Jenuwein T. 2016. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17:487–500
   [Google Scholar]
5. Asghar U, Witkiewicz AK, Turner NC, Knudsen ES 2015. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat. Rev. Drug Discov. 14:130–46
   [Google Scholar]
6. Babaian A, Romanish MT, Gagnier L, Kuo LY, Karimi MM et al. 2015. Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. Oncogene 35:2542–46
   [Google Scholar]
7. Baltimore D. 1970. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226:1209–11
   [Google Scholar]
8. Beck CR, Garcia-Perez JL, Badge RM, Moran JV 2011. LINE-1 elements in structural variation and disease. Annu. Rev. Genom. Hum. Genet. 12:187–215
   [Google Scholar]
9. Belancio VP, Roy-Engel AM, Deininger PL 2010. All y'all need to know ‘bout retroelements in cancer. Semin. Cancer Biol. 20:200–10
   [Google Scholar]
10. Bertoli C, Skotheim JM, de Bruin RAM 2013. Control of cell cycle transcription during G1 and S phases. Nat. Rev. Mol. Cell Biol. 14:518–28
    [Google Scholar]
11. Blaise S, de Parseval N, Benit L, Heidmann T 2003. Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. PNAS 100:13013–18
    [Google Scholar]
12. Boeke JD, Garfinkel DJ, Styles CA, Fink GR 1985. Ty elements transpose through an RNA intermediate. Cell 40:491–500
    [Google Scholar]
13. Boller K, Janssen O, Schuldes H, Tönjes RR, Kurth R 1997. Characterization of the antibody response specific for the human endogenous retrovirus HTDV/HERV-K. J. Virol. 71:4581–88
    [Google Scholar]
14. Bourc'his D, Bestor TH. 2004. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431:96–99
    [Google Scholar]
15. Brocks D, Schmidt CR, Daskalakis M, Jang HS, Shah NM et al. 2017. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat. Genet. 49:1052–60
    [Google Scholar]
16. Brouha B, Schustak J, Badge RM, Lutz-Prigge S, Farley AH et al. 2003. Hot L1s account for the bulk of retrotransposition in the human population. PNAS 100:5280–85
    [Google Scholar]
17. Cañadas I, Thummalapalli R, Kim JW, Kitajima S, Jenkins RW et al. 2018. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat. Med. 24:1143–50
    [Google Scholar]
18. Cherkasova E, Malinzak E, Rao S, Takahashi Y, Senchenko VN et al. 2011. Inactivation of the von Hippel-Lindau tumor suppressor leads to selective expression of a human endogenous retrovirus in kidney cancer. Oncogene 30:4697–706
    [Google Scholar]
19. Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C et al. 2015. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162:974–86
    [Google Scholar]
20. Chuong EB, Elde NC, Feschotte C 2016. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 351:1083–87
    [Google Scholar]
21. Chuong EB, Elde NC, Feschotte C 2017. Regulatory activities of transposable elements: from conflicts to benefits. Nat. Rev. Genet. 18:71–86
    [Google Scholar]
22. Colum PW, Chaillet JR, Timothy HB 1998. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet. 20:116–17
    [Google Scholar]
23. Cooper S, Dienstbier M, Hassan R, Schermelleh L, Sharif J et al. 2014. Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment. Cell Rep 7:1456–70
    [Google Scholar]
24. Coschi CH, Ishak CA, Gallo D, Marshall A, Talluri S et al. 2014. Haploinsufficiency of an RB–E2F1–condensin II complex leads to aberrant replication and aneuploidy. Cancer Discov 4:840–53
    [Google Scholar]
25. Cuellar TL, Herzner A-M, Zhang X, Goyal Y, Watanabe C et al. 2017. Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia. J. Cell Biol. 216:3535–49
    [Google Scholar]
26. De Cecco M, Ito T, Petrashen AP, Elias AE, Skvir NJ et al. 2019. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature 566:73–78
    [Google Scholar]
27. Deniger DC, Pasetto A, Robbins PF, Gartner JJ, Prickett TD et al. 2018. T-cell responses to TP53 “hotspot” mutations and unique neoantigens expressed by human ovarian cancers. Clin. Cancer Res. 24:5562–73
    [Google Scholar]
28. Dombroski BA, Mathias SL, Nanthakumar E, Scott AF, Kazazian HH 1991. Isolation of an active human transposable element. Science 254:1805–8
    [Google Scholar]
29. Doucet-O'Hare TT, Rodic N, Sharma R, Darbari I, Abril G et al. 2015. LINE-1 expression and retrotransposition in Barrett's esophagus and esophageal carcinoma. PNAS 112:E4894–900
    [Google Scholar]
30. Dougherty RM, Di Stefano HS 1966. Lack of relationship between infection with avian leukosis virus and the presence of COFAL antigen in chick embryos. Virology 29:586–95
    [Google Scholar]
31. Dougherty RM, Di Stefano HS, Roth FK 1967. Virus particles and viral antigens in chicken tissues free of infectious avian leukosis virus. PNAS 58:808–17
    [Google Scholar]
32. Ewing AD, Gacita A, Wood LD, Ma F, Xing D et al. 2015. Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution. Genome Res 25:1536–45
    [Google Scholar]
33. Flasch DA, Macia Á, Sánchez L, Ljungman M, Heras SR et al. 2019. Genome-wide de novo L1 retrotransposition connects endonuclease activity with replication. Cell 177:837–51
    [Google Scholar]
34. Gal-Yam EN, Egger G, Iniguez L, Holster H, Einarsson S et al. 2008. Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. PNAS 105:12979–84
    [Google Scholar]
35. Garfinkel DJ, Boeke JD, Fink GR 1985. Ty element transposition: reverse transcriptase and virus-like particles. Cell 42:507–17
    [Google Scholar]
36. Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J et al. 2003. Induction of tumors in mice by genomic hypomethylation. Science 300:489–92
    [Google Scholar]
37. Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J et al. 2017. CDK4/6 inhibition triggers anti-tumour immunity. Nature 548:471–75
    [Google Scholar]
38. Guler GD, Tindell CA, Pitti R, Wilson C, Nichols K et al. 2017. Repression of stress-induced LINE-1 expression protects cancer cell subpopulations from lethal drug exposure. Cancer Cell 32:221–37.e13
    [Google Scholar]
39. Hata K, Okano M, Lei H, Li E 2002. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129:1983–93
    [Google Scholar]
40. He Q, Kim H, Huang R, Lu W, Tang M et al. 2015. The Daxx/Atrx complex protects tandem repetitive elements during DNA hypomethylation by promoting H3K9 trimethylation. Cell Stem Cell 17:273–86
    [Google Scholar]
41. Hirano T. 2016. Condensin-based chromosome organization from bacteria to vertebrates. Cell 164:847–57
    [Google Scholar]
42. Howard G, Eiges R, Gaudet F, Jaenisch R, Eden A 2008. Activation and transposition of endogenous retroviral elements in hypomethylation induced tumors in mice. Oncogene 27:404–8
    [Google Scholar]
43. Hur S. 2019. Double-stranded RNA sensors and modulators in innate immunity. Annu. Rev. Immunol. 37:349–75
    [Google Scholar]
44. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M 1993. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363:558–61
    [Google Scholar]
45. Ishak CA, Classon M, De Carvalho DD 2018. Deregulation of retroelements as an emerging therapeutic opportunity in cancer. Trends Cancer 4:583–97
    [Google Scholar]
46. Ishak CA, Coschi CH, Roes MV, Dick FA 2017. Disruption of CDK-resistant chromatin association by pRB causes DNA damage, mitotic errors, and reduces Condensin II recruitment. Cell Cycle 16:1430–39
    [Google Scholar]
47. Ishak CA, Marshall AE, Passos DT, White CR, Kim SJ et al. 2016. An RB-EZH2 complex mediates silencing of repetitive DNA sequences. Mol. Cell 64:1074–87
    [Google Scholar]
48. Jacobs FMJ, Greenberg D, Nguyen N, Haeussler M, Ewing AD et al. 2014. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons. Nature 516:242–45
    [Google Scholar]
49. Jang HS, Shah NM, Du AY, Dailey ZZ, Pehrsson EC et al. 2019. Transposable elements drive widespread expression of oncogenes in human cancers. Nat. Genet. 51:611–17
    [Google Scholar]
50. Jin X, Ding D, Yan Y, Li H, Wang B et al. 2019. Phosphorylated RB promotes cancer immunity by inhibiting NF-κB activation and PD-L1 expression. Mol. Cell 73:22–35.e6
    [Google Scholar]
51. Jones PA, Ohtani H, Chakravarthy A, De Carvalho DD 2019. Epigenetic therapy in immune-oncology. Nat. Rev. Cancer 19:151–61
    [Google Scholar]
52. Kapitonov VV, Jurka J. 2005. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLOS Biol 3:e181
    [Google Scholar]
53. Karimi MM, Goyal P, Maksakova IA, Bilenky M, Leung D et al. 2011. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell 8:676–87
    [Google Scholar]
54. Kassiotis G, Stoye JP. 2016. Immune responses to endogenous retroelements: taking the bad with the good. Nat. Rev. Immunol. 16:207–19
    [Google Scholar]
55. Kazazian HH, Moran JV. 1998. The impact of L1 retrotransposons on the human genome. Nat. Genet. 19:19–24
    [Google Scholar]
56. Kazazian HH, Wong C, Youssoufian H, Scott AF, Phillips DG, Antonarakis SE 1988. Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature 332:164–66
    [Google Scholar]
57. Kraus B, Fischer K, Büchner SM, Wels WS, Löwer R et al. 2013. Vaccination directed against the human endogenous retrovirus-K envelope protein inhibits tumor growth in a murine model system. PLOS ONE 8:e72756
    [Google Scholar]
58. Kraus B, Fischer K, Sliva K, Schnierle BS 2014. Vaccination directed against the human endogenous retrovirus-K (HERV-K) gag protein slows HERV-K gag expressing cell growth in a murine model system. Virol. J. 11:58
    [Google Scholar]
59. Krishnamurthy J, Rabinovich BA, Mi T, Switzer KC, Olivares S et al. 2015. Genetic engineering of T cells to target HERV-K, an ancient retrovirus on melanoma. Clin. Cancer Res. 21:3241–51
    [Google Scholar]
60. Lamprecht B, Walter K, Kreher S, Kumar R, Hummel M et al. 2010. Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nat. Med. 16:571–79
    [Google Scholar]
61. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al. 2001. Initial sequencing and analysis of the human genome. Nature 409:860–921
    [Google Scholar]
62. Laumont CM, Daouda T, Laverdure J-P, Bonneil É, Caron-Lizotte O et al. 2016. Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames. Nat. Commun. 7:10238
    [Google Scholar]
63. Laumont CM, Vincent K, Hesnard L, Audemard É, Bonneil É et al. 2018. Noncoding regions are the main source of targetable tumor-specific antigens. Sci. Transl. Med. 10:eaau5516
    [Google Scholar]
64. Leadem BR, Kagiampakis I, Wilson C, Cheung TK, Arnott D et al. 2018. A KDM5 inhibitor increases global H3K4 trimethylation occupancy and enhances the biological efficacy of 5-aza-2′-deoxycytidine. Cancer Res 78:1127–39
    [Google Scholar]
65. Lee E, Iskow R, Yang L, Gokcumen O, Haseley P et al. 2012. Landscape of somatic retrotransposition in human cancers. Science 337:967–71
    [Google Scholar]
66. Levin HL, Moran JV. 2011. Dynamic interactions between transposable elements and their hosts. Nat. Rev. Genet. 12:615–27
    [Google Scholar]
67. Li E, Bestor TH, Jaenisch R 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–26
    [Google Scholar]
68. Liu M, Ohtani H, Zhou W, Ørskov AD, Charlet J et al. 2016. Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine. PNAS 113:10238–44
    [Google Scholar]
69. Liu M, Thomas SL, DeWitt AK, Zhou W, Madaj ZB et al. 2018a. Dual inhibition of DNA and histone methyltransferases increases viral mimicry in ovarian cancer cells. Cancer Res 78:5754–66
    [Google Scholar]
70. Liu M, Zhang L, Li H, Hinoue T, Zhou W et al. 2018b. Integrative epigenetic analysis reveals therapeutic targets to the DNA methyltransferase inhibitor SGI‐110 in hepatocellular carcinoma. Hepatology 68:1412–28
    [Google Scholar]
71. Lock FE, Babaian A, Zhang Y, Gagnier L, Kuah S et al. 2017. A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer. PLOS ONE 12:e0180659
    [Google Scholar]
72. Loo Yau H, Ettayebi I, De Carvalho DD 2019. The cancer epigenome: exploiting its vulnerabilities for immunotherapy. Trends Cell Biol 29:31–43
    [Google Scholar]
73. Lu X, Sachs F, Ramsay L, Jacques P-É, Göke J et al. 2014. The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nat. Struct. Mol. Biol. 21:423–25
    [Google Scholar]
74. Mager DL, Stoye JP. 2015. Mammalian endogenous retroviruses. Mobile DNA III N Craig, M Chandler, M Gellert, A Lambowitz, P Rice, S Sandmeyer 1079–100 Washington, DC: Am. Soc. Microbiol.
    [Google Scholar]
75. Malekzadeh P, Pasetto A, Robbins PF, Parkhurst MR, Paria BC et al. 2019. Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers. J. Clin. Investig. 129:1109–14
    [Google Scholar]
76. McClintock B. 1950. The origin and behavior of mutable loci in maize. PNAS 36:344–55
    [Google Scholar]
77. Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J et al. 1992. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res 52:643–45
    [Google Scholar]
78. Najafabadi HS, Mnaimneh S, Schmitges FW, Garton M, Lam KN et al. 2015. C2H2 zinc finger proteins greatly expand the human regulatory lexicon. Nat. Biotechnol. 33:555–62
    [Google Scholar]
79. O'Leary B, Finn RS, Turner NC 2016. Treating cancer with selective CDK4/6 inhibitors. Nat. Rev. Clin. Oncol. 13:417–30
    [Google Scholar]
80. Otto T, Sicinski P. 2017. Cell cycle proteins as promising targets in cancer therapy. Nat. Rev. Cancer 17:93–115
    [Google Scholar]
81. Percharde M, Lin C-J, Yin Y, Guan J, Peixoto GA et al. 2018. A LINE1-nucleolin partnership regulates early development and ESC identity. Cell 174:391–405.e19
    [Google Scholar]
82. Peters AH, O'Carroll D, Scherthan H, Mechtler K, Sauer S et al. 2001. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107:323–37
    [Google Scholar]
83. Pisanic TR, Asaka S, Lin S-F, Yen T-T, Sun H et al. 2018. Long interspersed nuclear element 1 retrotransposons become deregulated during the development of ovarian cancer precursor lesions. Am. J. Pathol. 189:513–20
    [Google Scholar]
84. Raviram R, Rocha PP, Luo VM, Swanzey E, Miraldi ER et al. 2018. Analysis of 3D genomic interactions identifies candidate host genes that transposable elements potentially regulate. Genome Biol 19:216
    [Google Scholar]
85. Rodic N, Sharma R, Sharma R, Zampella J, Dai L et al. 2014. Long interspersed element-1 protein expression is a hallmark of many human cancers. Am. J. Pathol. 184:1280–86
    [Google Scholar]
86. Rodic N, Steranka JP, Makohon-Moore A, Moyer A, Shen P et al. 2015. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma. Nat. Med. 21:1060–64
    [Google Scholar]
87. Rogan PK, Pan J, Weissman SM 1987. L1 repeat elements in the human epsilon-G gamma-globin gene intergenic region: sequence analysis and concerted evolution within this family. Mol. Biol. Evol. 4:327–42
    [Google Scholar]
88. Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N 2015. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160:48–61
    [Google Scholar]
89. Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A et al. 2015. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162:961–73
    [Google Scholar]
90. Rowe HM, Trono D. 2011. Dynamic control of endogenous retroviruses during development. Virology 411:273–87
    [Google Scholar]
91. Sacha JB, Kim I-J, Chen L, Ullah JH, Goodwin DA et al. 2012. Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic. J. Immunol. 189:1467–79
    [Google Scholar]
92. Saksouk N, Barth TK, Ziegler-Birling C, Olova N, Nowak A et al. 2014. Redundant mechanisms to form silent chromatin at pericentromeric regions rely on BEND3 and DNA methylation. Mol. Cell 56:580–94
    [Google Scholar]
93. Sheng W, LaFleur MW, Nguyen TH, Chen S, Chakravarthy A et al. 2018. LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell 174:549–63.e19
    [Google Scholar]
94. Simon M, Van Meter M, Ablaeva J, Ke Z, Gonzalez RS et al. 2019. LINE1 derepression in aged wild-type and SIRT6-deficient mice drives inflammation. Cell Metab 29:871–85.e5
    [Google Scholar]
95. Slotkin RK, Martienssen R. 2007. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet. 8:272–85
    [Google Scholar]
96. Stehelin D, Varmus HE, Bishop JM, Vogt PK 1976. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170–73
    [Google Scholar]
97. Stone ML, Chiappinelli KB, Li H, Murphy LM, Travers ME et al. 2017. Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden. PNAS 114:E10981–90
    [Google Scholar]
98. Strand M, Prolla TA, Liskay RM, Petes TD 1993. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365:274–76
    [Google Scholar]
99. Sultana T, van Essen D, Siol O, Bailly-Bechet M, Philippe C et al. 2019. The landscape of L1 retrotransposons in the human genome is shaped by pre-insertion sequence biases and post-insertion selection. Mol. Cell 74:555–70.e7
    [Google Scholar]
100. Takahashi Y, Harashima N, Kajigaya S, Yokoyama H, Cherkasova E et al. 2008. Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells. J. Clin. Investig. 118:1099–109
     [Google Scholar]
101. Tasselli L, Xi Y, Zheng W, Tennen RI, Odrowaz Z et al. 2016. SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence. Nat. Struct. Mol. Biol. 23:434–40
     [Google Scholar]
102. Taunton J, Hassig CA, Schreiber SL 1996. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272:408–11
     [Google Scholar]
103. Temin HM, Mizutani S. 1970. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–13
     [Google Scholar]
104. Thompson PJ, Macfarlan TS, Lorincz MC 2016. Long terminal repeats: from parasitic elements to building blocks of the transcriptional regulatory repertoire. Mol. Cell 62:766–76
     [Google Scholar]
105. Ting DT, Lipson D, Paul S, Brannigan BW, Akhavanfard S et al. 2011. Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331:593–96
     [Google Scholar]
106. Treangen TJ, Salzberg SL. 2012. Repetitive DNA and next-generation sequencing: computational challenges and solutions. Nat. Rev. Genet. 13:36–46
     [Google Scholar]
107. Walter M, Teissandier A, Perez-Palacios R, Bourc'his D 2016. An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. eLife 5:e11418
     [Google Scholar]
108. Wang-Johanning F, Rycaj K, Plummer JB, Li M, Yin B et al. 2012. Immunotherapeutic potential of anti-human endogenous retrovirus-K envelope protein antibodies in targeting breast tumors. J. Natl. Cancer Inst. 104:189–210
     [Google Scholar]
109. Weiss RA. 2006. The discovery of endogenous retroviruses. Retrovirology 3:67
     [Google Scholar]
110. Wolff EM, Byun H-M, Han HF, Sharma S, Nichols PW et al. 2010. Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer. PLOS Genet 6:e1000917
     [Google Scholar]
111. Wylie A, Jones AE, D'Brot A, Lu W-J, Kurtz P et al. 2015. p53 genes function to restrain mobile elements. Genes Dev 30:64–77
     [Google Scholar]
112. Yu P, Lübben W, Slomka H, Gebler J, Konert M et al. 2012. Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors. Immunity 37:867–79
     [Google Scholar]
113. Zhang H, Pandey S, Travers M, Sun H, Morton G et al. 2018. Targeting CDK9 reactivates epigenetically silenced genes in cancer. Cell 175:1244–58.e26
     [Google Scholar]
114. Zhang Y, Cheng TC, Huang G, Lu Q, Surleac MD et al. 2019a. Transposon molecular domestication and the evolution of the RAG recombinase. Nature 569:79–84
     [Google Scholar]
115. Zhang Y, Li T, Preissl S, Amaral ML, Grinstein JD et al. 2019b. Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. Nat. Genet. 51:1380–88
     [Google Scholar]
116. Zhou F, Krishnamurthy J, Wei Y, Li M, Hunt K et al. 2015. Chimeric antigen receptor T cells targeting HERV-K inhibit breast cancer and its metastasis through downregulation of Ras. Oncoimmunology 4:e1047582
     [Google Scholar]
117. Zhu Q, Hoong N, Aslanian A, Hara T, Benner C et al. 2018. Heterochromatin-encoded satellite RNAs induce breast cancer. Mol. Cell 70:842–53.e7
     [Google Scholar]
118. Zhu Q, Pao GM, Huynh AM, Suh H, Tonnu N et al. 2011. BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477:179–84
     [Google Scholar]