Chapter 47 : Mammalian Endogenous Retroviruses

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Mammalian Endogenous Retroviruses, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819217/9781555819200_Chap47-1.gif /docserver/preview/fulltext/10.1128/9781555819217/9781555819200_Chap47-2.gif


Mammalian genomes have accumulated millions of retrotransposed sequences during evolution. This material can be divided into long terminal repeat (LTR) retrotransposons that include the endogenous retroviruses (ERVs), as well as long and short retrotransposons lacking LTRs, known as LINEs and SINEs, respectively. ERVs are defined as inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. In this chapter we describe the discovery, classification, and origins of ERVs in mammals, consider cellular mechanisms that have evolved to control their expression, and discuss the biological consequences, both positive and negative from the host’s standpoint, of ERV inheritance.

Citation: Mager D, Stoye J. 2015. Mammalian Endogenous Retroviruses, p 1079-1100. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0009-2014
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

(A) Formation of ERVs. Exogenous retroviruses typically infect their host and spread to other individuals via horizontal transmission. When retroviruses infect and integrate into the genome of germ line cells, the provirus can be vertically transmitted and become endogenous to the host. ERVs can amplify in the host genome through reinfection or through intracellular retrotransposition (see text). (B) Basic structures of ERVs. Complete ERVs are essentially identical to the integrated proviruses of simple exogenous retroviruses; they contain two LTRs made up of unique 3′ (U3), repeat (R), and unique 5′ (U5) regions, a primer binding site (pbs) and polypurine tract (ppt), as well as a full complement of coding sequences (, , and ), splice donor (SD) and acceptor (SA) sites, and an RNA packaging signal (psi). Slimmed down” ERVs are elements lacking coding sequences compared to a complete ERV—here illustrated with a deletion in . “Substituted” ERVs are elements in which the ERV coding sequences have been replaced with nonviral sequences. “Solo LTRs” are single LTRs generated by homologous recombination between the two LTRs of a complete element.

Citation: Mager D, Stoye J. 2015. Mammalian Endogenous Retroviruses, p 1079-1100. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0009-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

ERV/LTR content in different species. Overall genomic fractions occupied by ERVs and solo LTRs in various species. Data were obtained from the RepeatMasker web site (http://www.repeatmasker.org/genomicDatasets/RMGenomicDatasets.html) and are updated from the original genome publications—for example, the human and mouse genome papers ( ) due to a more-sensitive repeat detection.

Citation: Mager D, Stoye J. 2015. Mammalian Endogenous Retroviruses, p 1079-1100. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0009-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Common ways in which retroviral insertions can affect genes. (A) Proviral elements are shown as thick lines, with arrows for the LTRs, and gene exons are numbered boxes with P showing the gene promoter. Retroviral elements inserted near genes can donate their LTR enhancers or promoters to affect gene expression. This mechanism occurs when new somatic retroviral insertions activate oncogenes. This mechanism also occurs in normal cells as an evolutionary adaptation and in mouse cells defective for LTR epigenetic silencing. This can occur even if only a solitary LTR remains. (B) When inserted in an intron, splice sites and polyA signals within ERVs can perturb splicing. Most of the documented germ line-detrimental ERV insertions in mice are due to this mechanism. (C) ERVs/LTRs located downstream of a gene or within an intron have the potential to promote antisense transcripts, possibly regulating the gene or causing premature polyadenylation. (D) Closely related LTRs/ERVs distributed across the genome (black triangles) that bind the same transcription factors can become exapted (shown as gray triangles) and regulate expression of sets of genes (gene A and C in this example), establishing a regulatory network.

Citation: Mager D, Stoye J. 2015. Mammalian Endogenous Retroviruses, p 1079-1100. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0009-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Independent instances of ERV Env domestication involved in placenta formation. (A) Domestication of Env proteins (which have natural fusogenic properties) can promote the formation of multinucleated tissue, as occurs in the developing placenta. Env syncytin-like molecules are shown as balls binding to receptors. (B) Schematic evolutionary tree showing different instances of ERV Env domestication (shown as arrows): Syncytin-A and Syncytin-B ( ), Syncytin-Ory1 ( ), Syncytin-1 ( ), Syncytin-2 ( ), Syncytin-Rum1 ( ), Fematrin-1 ( ), Syncytin-Car1 ( ), and Syncytin-Mar1 ( ).

Citation: Mager D, Stoye J. 2015. Mammalian Endogenous Retroviruses, p 1079-1100. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0009-2014
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Weiss RA . 2006. The discovery of endogenous retroviruses. Retrovirology 3 : 67. [PubMed] [CrossRef]
2. Lowy DR,, Rowe WP,, Teich N,, Hartley JW . 1971. Murine leukemia virus: high frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine. Science 174 : 155 156.[PubMed] [CrossRef]
3. Benveniste RE,, Todaro GJ . 1974. Multiple divergent copies of endogenous type C virogenes in mammalian cells. Nature 252 : 170 173.[PubMed] [CrossRef]
4. Boeke JD,, Stoye JP, . 1997. Retrotransposons, endogenous retroviruses and the evolution of retroelements, p 343 435. In Coffin JM,, Hughes SH,, Varmus HE (ed), Retroviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
5. Khan AS,, Ma W,, Ma Y,, Kumar A,, Williams DK,, Muller J,, Ma H,, Galvin TA . 2009. Proposed algorithm to investigate latent and occult viruses in vaccine cell substrates by chemical induction. Biologicals 37 : 196 201.[PubMed] [CrossRef]
6. Paprotka T,, Delviks-Frankenberry KA,, Cingoz O,, Martinez A,, Kung HJ,, Tepper CG,, Hu WS,, Fivash MJ Jr,, Coffin JM,, Pathak VK . 2011. Recombinant origin of the retrovirus XMRV. Science 333 : 97 101.[PubMed] [CrossRef]
7. Voisset C,, Weiss RA,, Griffiths DJ . 2008. Human RNA “rumor” viruses: the search for novel human retroviruses in chronic disease. Microbiol Mol Biol Rev 72 : 157 196.[PubMed] [CrossRef]
8. Callahan R,, Drohan W,, Tronick S,, Schlom J . 1982. Detection and cloning of human DNA sequences related to the mouse mammary tumor virus genome. Proc Natl Acad Sci U S A 79 : 5503 5507.[PubMed] [CrossRef]
9. Martin MA,, Bryan T,, Rasheed S,, Khan AS . 1981. Identification and cloning of endogenous retroviral sequences present in human DNA. Proc Natl Acad Sci U S A 78 : 4892 4896.[PubMed] [CrossRef]
10. Dunwiddie CT,, Resnick R,, Boyce-Jacino M,, Alegre JN,, Faras AJ . 1986. Molecular cloning and characterization of gag-, pol-, and env-related gene sequences in the ev chicken. J Virol 59 : 669 675.[PubMed]
11. Medstrand P,, Blomberg J . 1993. Characterization of novel reverse transcriptase encoding human endogenous retroviral sequences similar to type A and type B retroviruses: differential transcription in normal human tissues. J Virol 67 : 6778 6787.[PubMed]
12. Shih A,, Misra R,, Rush MG . 1989. Detection of multiple, novel reverse transcriptase coding sequences in human nucleic acids: relation to primate retroviruses. J Virol 63 : 64 75.[PubMed]
13. Tristem M,, Kabat P,, Lieberman L,, Linde S,, Karpas A,, Hill F . 1996. Characterization of a novel murine leukemia virus-related subgroup within mammals. J Virol 70 : 8241 8246.[PubMed]
14. Smit AFA . 1993. Identification of a new, abundant superfamily of mammalian LTR-retrotransposons. Nucl Acids Res 21 : 1863 1872.[PubMed] [CrossRef]
15. Smit AFA . 1996. The origin of interspersed repeats in the human genome. Curr Opin Genet Dev 6 : 743 748.[PubMed] [CrossRef]
16. Chimpanzee Sequencing and Analysis Consortium . 2005. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437 : 6987.[PubMed] [CrossRef]
17. International Chicken Genome Sequencing Consortium . 2004. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432 : 695716.[PubMed] [CrossRef]
18. International Human Genome Sequencing Consortium . 2001. Initial sequencing and analysis of the human genome. Nature 409 : 860921.[PubMed] [CrossRef]
19. International Mouse Genome Sequencing Consortium . 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420 : 520562.[PubMed] [CrossRef]
20. Lerat E . 2010. Identifying repeats and transposable elements in sequenced genomes: how to find your way through the dense forest of programs. Heredity 104 : 520 522.[PubMed] [CrossRef]
21. Sperber GO,, Airola T,, Jern P,, Blomberg J . 2007. Automated recognition of retroviral sequences in genomic data—RectoTector. Nucl Acids Res 35 : 4964 4976.[PubMed] [CrossRef]
22. Katzourakis A,, Gifford RJ . 2010. Endogenous viral elements in animal genomes. PLoS Genet 6 : e1001191. [PubMed] [CrossRef]
23. Magiorkinis G,, Gifford RJ,, Katzourakis A,, De Ranter J,, Belshaw R . 2012. Env-less endogenous retroviruses are genomic superspreaders. Proc Natl Acad Sci U S A 109 : 7385 7390.[PubMed] [CrossRef]
24. Hayward A,, Grabherr M,, Jern P . 2013. Broad-scale phylogenomics provides insights into retrovirus-host evolution. Proc Natl Acad Sci U S A 110 : 20146 20151.[PubMed] [CrossRef]
25. Stoye JP,, Coffin JM . 1987. The four classes of endogenous murine leukemia viruses: structural relationships and potential for recombination. J Virol 61 : 2659 2669.[PubMed]
26. Hohn O,, Hanke K,, Bannert N . 2013. HERV-K(HML-2), the best preserved family of HERVs: endogenisation, expression and implications in health and disease. Front Oncol 3 : 1 12.[PubMed] [CrossRef]
27. Katzourakis A,, Tristem M,, Pybus OG,, Gifford RJ . 2007. Discovery and analysis of the first endogenous lentivirus. Proc Natl Acad Sci U S A 104 : 6261 6265.[PubMed] [CrossRef]
28. Ribet D,, Harper F,, Dupressoir A,, Dewannieux M,, Pierron G,, Heidmann T . 2008. An infectious progenitor for the murine IAP retrotransposon: emergence of an intracellular genetic parasite from an ancient retrovirus. Genome Res 18 : 597 609.[PubMed] [CrossRef]
29. Ribet D,, Harper F,, Dewannieux M,, Pierron G,, Heidmann T . 2007. Murine MusD retrotransposon:structure and molecular evolution of an “intracellularized” retrovirus. J Virol 81 : 1888 1898.[PubMed] [CrossRef]
30. Swain A,, Coffin JM . 1992. Mechanism of transduction by retroviruses. Science 255 : 841 845.[PubMed] [CrossRef]
31. Sonigo P,, Wain-Hobson S,, Bougueleret L,, Tiollais P,, Jacob F,, Brulet P . 1987. Nucleotide sequence and evolution of ETn elements. Proc Natl Acad Sci U S A 84 : 3768 3771.[PubMed] [CrossRef]
32. Maksakova IA,, Romanish MT,, Gagnier L,, Dunn CA,, van de Lagemaat LN,, Mager DL . 2006. Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line. PLoS Genet 2 : e2. [PubMed] [CrossRef]
33. Benachenhou F,, Jern P,, Oja M,, Sperber G,, Blikstad V,, Somervuo P,, Kaski S,, Blomberg J . 2009. Evolutionary conservation of orthoretroviral long terminal repeats (LTRs) and ab initio detection of single LTRs in genomic data. PLoS One 4 : e5179. [PubMed] [CrossRef]
34. Belshaw R,, Watson J,, Katzourakis A,, Howe A,, Woolven-Allen J,, Burt A,, Tristem M . 2007. Rate of recombinational deletion among human endogenous retroviruses. J Virol 81 : 9437 9442.[PubMed] [CrossRef]
35. Seperack PK,, Strobel MC,, Corrow DJ,, Jenkins NA,, Copeland NG . 1988. Somatic and germ-line reverse mutation rates of the retrovirus-induced dilute coat-color mutation of DBA mice. Proc Natl Acad Sci U S A 85 : 189 192.[PubMed] [CrossRef]
36. de Parseval N,, Lazr V,, Casella JF,, Benit L,, Heidmann T . 2003. Survey of human genes of retroviral origin: identification and transcriptome of the genes with coding capacity for complete envelope proteins. J Virol 77 : 10414 10422.[PubMed] [CrossRef]
37. Villeson P,, Aagaard L,, Wiuf C,, Pedersen FS . 2004. Identification of endogenous retroviral reading frames in the human genome. Retrovirology 1 : 32. [PubMed] [CrossRef]
38. Jern P,, Stoye JP,, Coffin JM . 2007. Role of APOBEC3 in genetic diversity among endogenous murine leukemia viruses. PLoS Genet 3 : e183. [PubMed] [CrossRef]
39. Dewannieux M,, Harper F,, Richaud A,, Letzelter C,, Ribet D,, Pierron G,, Heidmann T . 2006. Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res 16 : 1548 1556.[PubMed] [CrossRef]
40. Lee YN,, Bieniasz PD . 2007. Reconstitution of an infectious human endogenous retrovirus. PLoS Pathog 3 : e10. [PubMed] [CrossRef]
41. Blomberg J,, Benachenhou F,, Blikstad V,, Sperber G,, Meyer J . 2009. Classification and nomenclature of endogenous retroviral sequences (ERVs): problems and recommendations. Gene 448 : 115 123.[PubMed] [CrossRef]
42. Meyer J,, Blomberg J,, Seal RL . 2011. A revised nomenclature for transcribed endogenous retroviral loci. Mob DNA 2 : 7. [PubMed] [CrossRef]
43. Tristem M . 2000. Identification and characterization of novel human endogenous retrovirus families by phylogenetic screening of the human genome mapping project database. J Virol 74 : 3715 3730.[PubMed] [CrossRef]
44. Henzy JE,, Johnson WE . 2013. Pushing the endogenous envelope. Phil Trans R Soc Lond B Biol Sci 368 : 20120506. [PubMed] [CrossRef]
45. Jurka J,, Kapitonov VV,, Pavlicek A,, Klonowski P,, Kohany O,, Walichiewicz J . 2005. Repbase Update, a database of eukaryotic repetitive elements. Cytogenet Genome Res 110 : 462 467.[PubMed] [CrossRef]
46. Bannert N,, Kurth R . 2006. The evolutionary dynamics of human endogenous retroviral families. Annu Rev. Genomics Hum Genet 7 : 149 173.[PubMed] [CrossRef]
47. de Parseval N,, Heidmann T . 2005. Human endogenous retroviruses: from infectious elements to human genes. Cytogenet Genome Res 110 : 318 332.[PubMed] [CrossRef]
48. Gifford R,, Tristem M . 2003. The evolution, distribution and diversity of endogenous retroviruses. Virus Genes 26 : 291 315.[CrossRef]
49. Zhuo X,, Rho M,, Feschotte C . 2013. Genome-wide characterization of endogenous retroviruses in the bat Myotis lucifugus reveals recent and diverse infections. J Virol 87 : 8493 8501.[PubMed] [CrossRef]
50. Magiorkinis G,, Belshaw R,, Katzourakis A . 2013. “There and back again”: revisiting the pathophysiological roles of human endogenous retroviruses in the post-genomic era. Phil Trans R Soc Lond B Biol Sci 368 : 20120504. [PubMed] [CrossRef]
51. Gilbert C,, Feschotte C . 2010. Genomic fossils calibrate the long term evolution of hepadnaviruses. PLoS Biol 8 : e1000495. [PubMed] [CrossRef]
52. Goodchild NL,, Wilkinson DA,, Mager DL . 1993. Recent evolutionary expansion of a subfamily of RTVL-H human endogenous retrovirus-like elements. Virology 196 : 778 788.[PubMed] [CrossRef]
53. Hughes JF,, Coffin JM . 2005. Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome. Genetics 171 : 1183 1194.[PubMed] [CrossRef]
54. Stoye JP . 2012. Studies of endogenous retroviruses reveal a continuing evolutionary saga. Nat Rev Microbiol 10 : 395 406.[PubMed]
55. Lee A,, Nolan A,, Watson J,, Tristem M . 2013. Identification of an ancient endogenous retrovirus, predating the divergence of placental animals. Phil Trans R Soc Lond B Biol Sci 368 : 20120503. [PubMed] [CrossRef]
56. Katzourakis A,, Rambaut A,, Pybus OG . 2005. The evolutionary dynamics of endogenous retroviruses. Trends Microbiol 13 : 463 468.[PubMed] [CrossRef]
57. Stocking C,, Kozak CA . 2008. Murine endogenous retroviruses. Cell Mol Life Sci 65 : 3383 3398.[PubMed] [CrossRef]
58. Subramanian RP,, Wildschutte JH,, C R,, Coffin JM . 2011. Identification, characterization, and comparative genomic distribution of the HERV-K(HML-2) group of human endogenous retroviruses. Retrovirology 8 : 90. [PubMed] [CrossRef]
59. Soriano P,, Jaenisch R . 1986. Retroviruses as probes for mammalian development: allocation of cells to the somatic and germ cell linages. Cell 46 : 19 29.[PubMed] [CrossRef]
60. Rowe WP,, Kozak CA . 1980. Germ-line reinsertions of AKR murine leukemia virus genomes in AKV-1 congenic mice. Proc Natl Acad Sci U S A 77 : 4871 4874.[PubMed] [CrossRef]
61. Lock LF,, Keshet E,, Gilbert DJ,, Jenkins NA,, Copeland NG . 1988. Studies on the mechanism of spontaneous germline ecotropic provirus acquisition in mice. EMBO J 7 : 4169 4177.[PubMed]
62. Simmons GS,, Young PR,, Hanger JJ,, Jones K,, Clarke D,, McKee JJ,, Meers J . 2012. Prevalence of koala retrovirus in geographically diverse populations in Australia. Aust Vet J 90 : 404 409.[PubMed] [CrossRef]
63. Tarlinton RE,, Meers J,, Young PR . 2006. Retroviral invasion of the koala genome. Nature 442 : 79 81.[PubMed] [CrossRef]
64. Xu W,, Stadler CK,, Gorman K,, Jensen N,, Kim DH,, Zheng H,, Tang S,, Switzer WM,, Pye GW,, Eiden MV . 2013. An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo. Proc Natl Acad Sci U S A 119 : 11547 11552.[PubMed] [CrossRef]
65. Avila-Arcos M,, Ho SYW,, Ishida Y,, Nikolaidis N,, Tsangaras K,, Hönig K,, Medina R,, Rasmussen M,, Fordyce SL,, Calvignac-Spencer S,, Willersley E,, Gilbert MTP,, Helgen KM,, Roca AL,, Greenwood AD . 2013. One hundred twenty years of koala retrovirus evolution determined from museum skins. Mol Biol Evol 30 : 299 304.[PubMed] [CrossRef]
66. Arias JF,, Koyama T,, Kinomoto M,, Tokunaga K . 2012. Retroelements versus apobec3 family members: no great escape from the magnificent seven. Front Microbiol 3 : 275. [PubMed] [CrossRef]
67. Crichton JH,, Dunican DS,, Maclennan M,, Meehan RR,, Adams IR . 2014. Defending the genome from the enemy within: mechanisms of retrotransposon suppression in the mouse germline. Cell Mol Life Sci 71 : 1581 1605.[PubMed] [CrossRef]
68. Maksakova I,, Mager D,, Reiss D . 2008. Keeping active endogenous retroviral-like sequences in check: the epigenetic perspective. Cell Mol Life Sci 65 : 3329 3347.[PubMed] [CrossRef]
69. Rowe HM,, Trono D . 2011. Dynamic control of endogenous retroviruses during development. Virology 411 : 273 287.[PubMed] [CrossRef]
70. Wolf D,, Goff SP . 2008. Host restriction factors blocking retroviral replication. Annu Rev Gen 42 : 143 163.[PubMed] [CrossRef]
71. Leung DC,, Lorincz MC . 2012. Silencing of endogenous retroviruses: when and why do histone marks predominate? Trends Biochem Sci 37 : 127 133.[PubMed] [CrossRef]
72. Law JA,, Jacobsen SE . 2010. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11 : 204 220.[PubMed] [CrossRef]
73. 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 : 404 408.[PubMed] [CrossRef]
74. Jaenisch R,, Schnieke A,, Harbers K . 1985. Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues. Proc Natl Acad Sci 82 : 1451 1445.[PubMed] [CrossRef]
75. Walsh CP,, Chaillet JR,, Bestor TH . 1998. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet 20 : 116 117.[PubMed] [CrossRef]
76. Bourc’his D,, Bestor TH . 2004. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431 : 96 99.[PubMed] [CrossRef]
77. Brûlet P,, Condamine H,, Jacob F . 1985. Spatial distribution of transcripts of the long repeated ETn sequence during early mouse embryogenesis. Proc Natl Acad Sci U S A 82 : 2054 2058.[PubMed] [CrossRef]
78. Peaston AE,, Evsikov AV,, Graber JH,, de Vries WN,, Holbrook AE,, Solter D,, Knowles BB . 2004. Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell 7 : 597 606.[PubMed] [CrossRef]
79. Li E,, Bestor TH,, Jaenisch R . 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69 : 915 926.[CrossRef]
80. Seifarth W,, Frank O,, Zeilfelder U,, Spiess B,, Greenwood AD,, Hehlmann R,, Leib-Mösch C . 2005. Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray. J Virol 79 : 341 352.[PubMed] [CrossRef]
81. Lavie L,, Kitova M,, Maldener E,, Meese E,, Mayer J . 2005. CpG methylation directly regulates transcriptional activity of the human endogenous retrovirus family HERV-K(HML-2). J Virol 79 : 876 883.[PubMed] [CrossRef]
82. Reiss D,, Zhang Y,, Mager DL . 2007. Widely variable endogenous retroviral methylation levels in human placenta. Nucleic Acids Res 35 : 4743 4754.[PubMed] [CrossRef]
83. Schulz WA,, Steinhoff C,, Florl AR . 2006. Methylation of endogenous human retroelements in health and disease. Curr Top Microbiol Immunol 310 : 211 250.[PubMed] [CrossRef]
84. Stengel S,, Fiebig U,, Kurth R,, Denner J . 2010. Regulation of human endogenous retrovirus-K expression in melanomas by CpG methylation. Genes Chromosomes Cancer 49 : 401 411.[PubMed] [CrossRef]
85. Szpakowski S,, Sun X,, Lage JM,, Dyer A,, Rubinstein J,, Kowalski D,, Sasaki C,, Costa J,, Lizardi PM . 2009. Loss of epigenetic silencing in tumors preferentially affects primate-specific retroelements. Gene 448 : 151 167.[PubMed] [CrossRef]
86. Xie M,, Hong C,, Zhang B,, Lowdon RF,, Xing X,, Li D,, Zhou X,, Lee HJ,, Maire CL,, Ligon KL,, Gascard P,, Sigaroudinia M,, Tlsty TD,, Kadlecek T,, Weiss A,, O’Geen H,, Farnham PJ,, Madden PAF,, Mungall AJ,, Tam A,, Kamoh B,, Cho S,, Moore R,, Hirst M,, Marra MA,, Costello JF,, Wang T . 2013. DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nat Genet 45 : 836 841.[PubMed] [CrossRef]
87. Meunier J,, Khelifi A,, Navratil V,, Duret L . 2005. Homology-dependent methylation in primate repetitive DNA. Proc Natl Sci Adad U S A 102 : 5471 5476.[PubMed] [CrossRef]
88. Aravin AA,, Bourc’his D . 2008. Small RNA guides for de novo DNA methylation in mammalian germ cells. Genes Dev 22 : 970 975.[PubMed] [CrossRef]
89. Yang N,, Kazazian HH . 2006. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nat Struct Mol Biol 13 : 763 771.[PubMed] [CrossRef]
90. Shilatifard A . 2006. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75 : 243 269.[PubMed] [CrossRef]
91. Mikkelsen TS,, Ku M,, Jaffe DB,, Issac B,, Lieberman E,, Giannoukos G,, Alvarez P,, Brockman W,, Kim T-K,, Koche RP,, Lee W,, Mendenhall E,, O/’Donovan A,, Presser A,, Russ C,, Xie X,, Meissner A,, Wernig M,, Jaenisch R,, Nusbaum C,, Lander ES,, Bernstein BE . 2007. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448 : 553 560.[PubMed] [CrossRef]
92. Matsui T,, Leung D,, Miyashita H,, Maksakova I,, Miyachi H,, Kimura H,, Tachibana M,, Lorincz MC,, Shinkai Y . 2010. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature 464 : 927 931.[PubMed] [CrossRef]
93. Rowe H,, Jakobsson J,, Mesnard D,, Rougemont J,, Reynard S,, Aktas T,, Maillard P,, Layard-Liesching H,, Verp S,, Marquis J,, Spitz F,, Constam D,, Trono D . 2010. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463 : 237 240.[PubMed] [CrossRef]
94. Karimi MM,, Goyal P,, Maksakova IA,, Bilenky M,, Leung D,, Tang JX,, Shinkai Y,, Mager DL,, Jones S,, Hirst M,, Lorincz MC . 2011. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell 8 : 676 687.[PubMed] [CrossRef]
95. Thomas JH,, Schneider S . 2011. Coevolution of retroelements and tandem zinc finger genes. Genome Res 21 : 1800 1812.[PubMed] [CrossRef]
96. Wolf D,, Goff SP . 2009. Embryonic stem cells use ZFP809 to silence retroviral DNAs. Nature 458 : 1201 1204.[PubMed] [CrossRef]
97. Maksakova IA,, Thompson PJ,, Goyal P,, Jones SJ,, Singh PB,, Karimi MM,, Lorincz MC . 2013. Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells. Epigenetics Chromatin 6 : 15. [PubMed] [CrossRef]
98. Macfarlan TS,, Gifford WD,, Agarwal S,, Driscoll S,, Lettieri K,, Wang J,, Andrews SE,, Franco L,, Rosenfeld MG,, Ren B,, Pfaff SL . 2011. Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A. Genes Dev 25 : 594 607.[PubMed] [CrossRef]
99. Leeb M,, Pasini D,, Novatchkova M,, Jaritz M,, Helin K,, Wutz A . 2010. Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev 24 : 265 276.[PubMed] [CrossRef]
100. Huda A,, Bowen NJ,, Conley AB,, Jordan IK . 2011. Epigenetic regulation of transposable element derived human gene promoters. Gene 475 : 39 48.[PubMed] [CrossRef]
101. Rowe HM,, Kapopoulou A,, Corsinotti A,, Fasching L,, Macfarlan TS,, Tarabay Y,, Viville SP,, Jakobsson J,, Pfaff SL,, Trono D . 2013. TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells. Genome Res 23 : 452 461.[PubMed] [CrossRef]
102. Rebollo R,, Miceli-Royer K,, Zhang Y,, Farivar S,, Gagnier L,, Mager DL . 2012. Epigenetic interplay between mouse endogenous retroviruses and host genes. Genome Biol 13 : R89. [PubMed] [CrossRef]
103. Ward MC,, Wilson MD,, Barbosa-Morais NL,, Schmidt D,, Stark R,, Pan Q,, Schwalie PC,, Menon S,, Lukk M,, Watt S,, Thybert D,, Kutter C,, Kirschner K,, Flicek P,, Blencowe BJ,, Odom DT . 2013. Latent regulatory potential of human-specific repetitive elements. Mol Cell 49 : 262 272.[PubMed] [CrossRef]
104. Bieniasz PD . 2004. Intrinsic immunity: a front-line defense against viral attack. Nat Immunol 5 : 1109 1115.[PubMed] [CrossRef]
105. Malim MH,, Bieniasz PD . 2012. HIV restriction factors and mechanisms of evasion. Cold Spring Harb Perspect Med 2 : a006940. [PubMed] [CrossRef]
106. Sheehy AM,, Gaddis NC,, Choi JD,, Malim MH . 2002. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418 : 646 650.[PubMed] [CrossRef]
107. Malim MH . 2009. APOBEC proteins and intrinsic resistance to HIV-1 infection. Phil Trans R Soc Lond B Biol Sci 364 : 675 687.[PubMed] [CrossRef]
108. Stremlau M,, Owens CM,, Perron MJ,, Kiessling M,, Autissler P,, Sodroski J . 2004. The cytoplasmic body component TRIM5a restricts HIV-1 infection in Old World monkeys. Nature 427 : 848 853.[PubMed] [CrossRef]
109. Nisole S,, Stoye JP,, Saïb A . 2005. Trim family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 3 : 799 808.[PubMed] [CrossRef]
110. Sanz-Ramos M,, Stoye JP . 2013. Capsid-binding retrovirus restriction factors: discovery, restriction specificity and implications for the development of novel therapeutics. J Gen Virol 94 : 2587 2898.[PubMed] [CrossRef]
111. Neil SJD,, Zang T,, Bieniasz PD . 2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451 : 425 430.[PubMed] [CrossRef]
112. Goldstone DC,, Ennis-Adeniran V,, Hedden JJ,, Groom HC,, Rice GI,, Christodoulou E,, Walker PA,, Kelly G,, Haire LF,, Yap MW,, de Carvalho LP,, Stoye JP,, Crow YJ,, Taylor IA,, Webb M . 2011. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 480 : 379 382.[PubMed] [CrossRef]
113. Koito A,, Ikeda T . 2011. Intrinsic restriction activity of AID/APOBEC family of enzymes against the mobility of retroelements. Mob Genet Elements 1 : 197 202.[PubMed] [CrossRef]
114. Haran-Ghera N,, Peled A,, Brightman BK,, Fan H . 1993. Lymphomagenesis in AKR. Fv-1 b congenic mice. Cancer Res 53 : 3433 3438.[PubMed]
115. Kozak CA . 2013. Evolution of different antiviral strategies in wild mouse populations exposed to different gammaretroviruses. Curr Opin Virol 3 : 657 663.[PubMed] [CrossRef]
116. Rosenberg N,, Jolicoeur P, . 1997. Retroviral pathogenesis, p 475 586. In Coffin JM,, Hughes SH,, Varmus H (ed), Retroviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
117. Kool J,, Berns A . 2009. High-throughput insertional mutagenesis screens in mice to identify oncogenic networks. Nat Rev Cancer 9 : 389 399.[PubMed] [CrossRef]
118. Stoye JP,, Moroni C,, Coffin JM . 1991. Virological events leading to spontaneous AKR thymomas. J Virol 65 : 1273 1285.[PubMed]
119. Ishihara H,, Tanaka I,, Wan H,, Nojima K,, Yoshida K . 2004. Retrotransposition of limited deletion type of intracisternal A-particle elements in the myeloid leukemia cells of C3H/He mice. J Radiat Res (Tokyo) 45 : 25 32.[CrossRef]
120. De Smet C,, Loriot A . 2010. DNA hypomethylation in cancer: Epigenetic scars of a neoplastic journey. Epigenetics 5 : 206 213.[PubMed] [CrossRef]
121. Romanish MT,, Cohen CJ,, Mager DL . 2010. Potential mechanisms of endogenous retroviral-mediated genomic instability in human cancer. Semin Cancer Biol 20 : 246 253.[PubMed] [CrossRef]
122. Chen T,, Meng Z,, Gan Y,, Wang X,, Xu F,, Gu Y,, Xu X,, Tang J,, Zhou H,, Zhang X,, Gan X,, Van Ness C,, Xu G,, Huang L,, Zhang X,, Fang Y,, Wu J,, Zheng S,, Jin J,, Huang W,, Xu R . 2013. The viral oncogene Np9 acts as a critical molecular switch for co-activating beta-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells. Leukemia 27 : 1469 1478.[PubMed] [CrossRef]
123. Galli UM,, Sauter M,, Lecher B,, Maurer S,, Herbst H,, Roemer K,, Mueller-Lantzsch N . 2005. Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors. Oncogene 24 : 3223 3228.[PubMed] [CrossRef]
124. Lamprecht B,, Walter K,, Kreher S,, Kumar R,, Hummel M,, Lenze D,, Kochert K,, Bouhlel MA,, Richter J,, Soler E,, Stadhouders R,, Johrens K,, Wurster KD,, Callen DF,, Harte MF,, Giefing M,, Barlow R,, Stein H,, Anagnostopoulos I,, Janz M,, Cockerill PN,, Siebert R,, Dorken B,, Bonifer C,, Mathas S . 2010. Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nat Med 16 : 571 579.[PubMed] [CrossRef]
125. Medstrand P,, van de Lagemaat LN,, Mager DL . 2002. Retroelement distributions in the human genome: variations associated with age and proximity to genes. Genome Res 12 : 1483 1495.[PubMed] [CrossRef]
126. Smit AF . 1999. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr Opin Genet Dev 9 : 657 663.[PubMed] [CrossRef]
127. Zhang Y,, Romanish MT,, Mager DL . 2011. Distributions of transposable elements reveal hazardous zones in mammalian introns. PLoS Comput Biol 7 : e1002046. [PubMed] [CrossRef]
128. Druker R,, Bruxner TJ,, Lehrbach NJ,, Whitelaw E . 2004. Complex patterns of transcription at the insertion site of a retrotransposon in the mouse. Nucl Acids Res 32 : 5800 5808.[PubMed] [CrossRef]
129. Li J,, Akagi K,, Hu Y,, Trivett AL,, Hlynialuk CJ,, Swing DA,, Volfovsky N,, Morgan TC,, Golubeva Y,, Stephens RM,, Smith DE,, Symer DE . 2012. Mouse endogenous retroviruses can trigger premature transcriptional termination at a distance. Genome Res 22 : 870 884.[PubMed] [CrossRef]
130. Conley AB,, Miller WJ,, Jordan IK . 2008. Human cis natural antisense transcripts initiated by transposable elements. Trends Genet 24 : 53 56.[PubMed] [CrossRef]
131. Morgan HD,, Sutherland HGE,, Martin DIK,, Whitelaw E . 1999. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23 : 314 318.[PubMed] [CrossRef]
132. Rakyan VK,, Chong S,, Champ ME,, Cuthbert PC,, Morgan HD,, Luu KV,, Whitelaw E . 2003. Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A 100 : 2538 2543.[PubMed] [CrossRef]
133. Rakyan VK,, Blewitt ME,, Druker R,, Preis JI,, Whitelaw E . 2002. Metastable epialleles in mammals. Trends Genet 18 : 348 351.[PubMed] [CrossRef]
134. Blewitt ME,, Vickaryous NK,, Paldi A,, Koseki H,, Whitelaw E . 2006. Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet 2 : e49. [PubMed] [CrossRef]
135. Baudino L,, Yoshinobu K,, Morito N,, Santiago-Raber M-L,, Izui S . 2010. Role of endogenous retroviruses in murine SLE. Autoimmun Reviews 10 : 27 34.[PubMed] [CrossRef]
136. Young GR,, Eksmond U,, Salcedo R,, Alexopoulou L,, Stoye JP,, Kassiotis G . 2012. Resurrection of endogenous retroviruses in antibody-deficient mice. Nature 491 : 774 778.[PubMed]
137. Sasai M,, Yamamoto M . 2013. Pathogen recognition receptors: ligands and signaling pathways by toll-like receptors. Int Rev Immunol 32 : 116 133.[PubMed] [CrossRef]
138. Yu P,, Lubben W,, Slomka H,, Gebler J,, Konert M,, Cai C,, Neubrandt L,, Prazeres da Costa O,, Paul S,, Dehnert S,, Dohne K,, Thanisch M,, Storsberg S,, Wiegand L,, Kaufmann A,, Nain M,, Quintanilla-Martinez L,, Bettio S,, Schnierle B,, Kolesnikova L,, Becker S,, Schnare M,, Bauer S . 2012. Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors. Immunity 37 : 867 879.[PubMed] [CrossRef]
139. Cherkasova E,, Weisman Q,, Childs RW . 2012. Endogenous retroviruses as targets for antitumor immunity in renal cell cancer and other tumors. Front Oncol 3 : 243. [PubMed]
140. Antony JM,, DesLauriers AM,, Bhat RK,, Ellestad KK,, Power C . 2011. Human endogenous retroviruses and multiple sclerosis: Innocent bystanders or disease determinants? Biochim Biophys Acta 1812 : 162 176.[PubMed] [CrossRef]
141. Balada E,, Vilardell-Tarrés M,, Ordi-Ros J . 2010. Implication of human endogenous retroviruses in the development of autoimmune diseases. Int Rev Immunol 29 : 351 370.[PubMed] [CrossRef]
142. Perl A,, Fernandez D,, Telarico T,, Phillips PE . 2010. Endogenous retroviral pathogenesis in lupus. Curr Opin Rheumatol 22 : 483 492.[PubMed] [CrossRef]
143. Venables PJW,, Brookes SM,, Griffiths D,, Weiss RA,, Boyd MT . 1995. Abundance of an endogenous retroviral envelope protein in placental trophoblasts suggests a biological function. Virology 211 : 589 592.[PubMed] [CrossRef]
144. de Parseval N,, Heidmann T . 1998. Physiological knockout of the envelope gene of the single-copy ERV-3 human endogenous retrovirus in a fraction of the Caucasian population. J Virol 72 : 3442 3445.[PubMed]
145. Blond JL,, Lavillette D,, Cheynet V,, Bouton O,, Oriol G,, Chapel-Fernandes S,, Mandrand B,, Mallet F,, Cosser F-L . 2000. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 74 : 3321 3329.[PubMed] [CrossRef]
146. Mi S,, Lee X,, Li X,, Veldman GM,, Finnerty H,, Racie L,, LaVallie E,, Tang XY,, Edouard P,, Howes S,, Keith JC Jr,, McCoy JM . 2000. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403 : 785 789.[PubMed] [CrossRef]
147. Blaise S,, de Parseval N,, Bénit L,, Heidmann T . 2003. Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci U S A 100 : 13013 13018.[PubMed] [CrossRef]
148. Vargas A,, Moreau J,, Landry S,, LeBellego F,, Toutaily C,, Rassart E,, Lafond J,, Barbeau B . 2009. Sybcytin-2 plays an important role in the fusion of human trophoblast cells. J Mol Biol 392 : 301 308.[PubMed] [CrossRef]
149. Dupressoir A,, Vernochet C,, Bawa O,, Harper F,, Pierron G,, Opolon P,, Heidmann T . 2009. Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene. Proc Natl Acad Sci U S A 106 : 12127 12132.[PubMed] [CrossRef]
150. Dupressoir A,, Vernochet C,, Harper F,, Guegan J,, Dessen P,, Pierron G,, Heidmann T . 2011. A pair of co-opted retroviral envelope syncytin genes is required for formation of the two-layered murine placental syncytiotrophoblast. Proc Natl Acad Sci U S A 108 : E1164 E1173.[PubMed] [CrossRef]
151. Lavialle C,, Cornelis G,, Dupressoir A,, Esnault C,, Heidmann O,, Vernochet C,, Heidmann T . 2013. Paleovirology of ‘syncytins’, retroviral env genes exapted for a role in placentation. Phil Trans R Soc Lond B Biol Sci 368 : 20120507. [PubMed] [CrossRef]
152. Lilly F . 1970. Fv- 2: Identification and location of a second gene governing the spleen focus response to Friend leukemia virus in mice. J Natl Cancer Inst 45 : 163 169.[PubMed]
153. Best S,, Le Tissier P,, Towers G,, Stoye JP . 1996. Positional cloning of the mouse retrovirus restriction gene Fv1 . Nature 382 : 826 829.[PubMed] [CrossRef]
154. Best S,, Le Tissier PR,, Stoye JP . 1997. Endogenous retroviruses and the evolution of resistance to retroviral infection. Trends Microbiol 4 : 313 318.[PubMed] [CrossRef]
155. Dodding MP,, Bock M,, Yap MW,, Stoye JP . 2005. Capsid processing requirements for abrogation of Fv1 and Ref1 restriction. J Virol 79 : 10571 10577.[PubMed] [CrossRef]
156. McDougall AS,, Terry A,, Tzavaras T,, Cheney C,, Rojko J,, Neil JC . 1994. Defective endogenous proviruses are expressed in feline lymphoid cells: evidence for a role in natural resistance to subgroup B feline leukemia virus. J Virol 68 : 2151 2160.[PubMed]
157. Odaka T,, Ikeda H,, Akatsuka T . 1980. Restricted expression of endogenous N-tropic XC-positive leukemia virus in hybrids between G and AKR mice: an effect of the Fv-4r gene. Int J Cancer 25 : 757 762.[PubMed] [CrossRef]
158. Wu T,, Yan Y,, Kozac CA . 2005. Rmcf2, a xenotropic provirus in the Asian mouse species Mus castaneus, blocks infection by mouse gammaretroviruses. J Virol 79 : 9677 9684.[PubMed] [CrossRef]
159. Young GR,, Ploquin MJ,, Eksmond U,, Wadwa M,, Stoye JP,, Kassiotis G . 2012. Negative selection by an endogenous retrovirus promotes a higher-avidity CD4+ T cell response to retroviral antigen. PLoS Pathog 8 : e1002709. [PubMed] [CrossRef]
160. Arnaud F,, Murcia PR,, Palmarini M . 2007. Mechanisms of late restriction induced by an endogenous retrovirus. J Virol 81 : 11441 11451.[PubMed] [CrossRef]
161. Acha-Orbea H,, Held W,, Wanders GA,, Shakhov AN,, Scarpellino L,, Lees RK,, MacDonald HR . 1993. Exogenous and endogenous mouse mammary tumor virus superantigens. Immunol Rev 131 : 5 25.[PubMed] [CrossRef]
162. Czarneski J,, Rassa JC,, Ross SR . 2003. Mouse mammary tumor virus and the immune system. Immunol Res 27 : 469 480.[PubMed] [CrossRef]
163. Frankel WN,, Rudy C,, Coffin JM,, Huber BT . 1991. Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice. Nature 349 : 526 528.[PubMed] [CrossRef]
164. Rebollo R,, Farivar S,, Mager DL . 2012. C-GATE—catalogue of genes affected by transposable elements. Mob DNA 3 : 9. [PubMed] [CrossRef]
165. Samuelson LC,, Phillips RS,, Swanberg LJ . 1996. Amylase gene structures in primates: retroposon insertions and promoter evolution. Mol Biol Evol 13 : 767 779.[PubMed] [CrossRef]
166. Ramakrishnan C,, Robins DM . 1997. Steroid hormone responsiveness of a family of closely related mouse proviral elements. Mamm Genome 8 : 811 817.[PubMed] [CrossRef]
167. Stavenhagen JB,, Robins DM . 1988. An ancient provirus has imposed androgen regulation on the adjacent mouse sex-limited protein gene. Cell 55 : 247 254.[PubMed] [CrossRef]
168. Pi W,, Zhu X,, Wu M,, Wang Y,, Fulzele S,, Eroglu A,, Ling J,, Tuan D . 2010. Long-range function of an intergenic retrotransposon. Proc Natl Acad Sci U S A 107 : 12992 12997.[PubMed] [CrossRef]
169. Beyer U,, Moll-Rocek J,, Moll UM,, Dobbelstein M . 2011. Endogenous retrovirus drives hitherto unknown proapoptotic p63 isoforms in the male germ line of humans and great apes. Proc Natl Acad Sci U S A 108 : 3624 3629.[PubMed] [CrossRef]
170. Cohen CJ,, Lock WM,, Mager DL . 2009. Endogenous retroviral LTRs as promoters for human genes: a critical assessment. Gene 448 : 105 114.[PubMed] [CrossRef]
171. Conley AB,, Piriyapongsa J,, Jordan IK . 2008. Retroviral promoters in the human genome. Bioinformatics 24 : 1563 1567.[PubMed] [CrossRef]
172. van de Lagemaat LN,, Landry J-R,, Mager DL,, Medstrand P . 2003. Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet 19 : 530 536.[PubMed] [CrossRef]
173. Banville D,, Boie Y . 1989. Retroviral long terminal repeat is the promoter of the gene encoding the tumor-associated calcium-binding protein oncomodulin in the rat. Journal of Molecular Biology 207 : 481 490.[PubMed] [CrossRef]
174. Romanish MT,, Lock WM,, van de Lagemaat LN,, Dunn CA,, Mager DL . 2007. Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution. PLoS Genetics 3 : e10. [PubMed] [CrossRef]
175. Conley A,, Jordan I . 2012. Cell type-specific termination of transcription by transposable element sequences. Mob DNA 3 : 15. [PubMed] [CrossRef]
176. Bourque G . 2009. Transposable elements in gene regulation and in the evolution of vertebrate genomes. Curr Opin Genet Dev 19 : 607 612.[PubMed] [CrossRef]
177. Feschotte C . 2008. Transposable elements and the evolution of regulatory networks. Nat Rev Genet 9 : 397 405.[PubMed] [CrossRef]
178. Rebollo R,, Romanish MT,, Mager DL . 2012. Transposable Elements: An Abundant and Natural Source of Regulatory Sequences for Host Genes. Annu Rev Genet 46 : 21 42.[PubMed] [CrossRef]
179. McClintock B . 1956. Controlling elements and the gene. Cold Spring Harb Symp Quant Biol 21 : 197 216.[PubMed] [CrossRef]
180. Britten RJ,, Davidson EH . 1969. Gene regulation for higher cells: a theory. Science 165 : 349 357.[PubMed] [CrossRef]
181. Thornburg BG,, Gotea V,, Makalowski W . 2006. Transposable elements as a significant source of transcription regulating signals. Gene 365 : 104 110.[PubMed] [CrossRef]
182. Kunarso G,, Chia NY,, Jeyakani J,, Hwang C,, Lu X,, Chan YS,, Ng HH,, Bourque G . 2010. Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet 42 : 631 634.[PubMed] [CrossRef]
183. Wang T,, Zeng J,, Lowe CB,, Sellers RG,, Salama SR,, Yang M,, Burgess SM,, Brachmann RK,, Haussler D . 2007. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc Natl Acad Sci U S A 104 : 18613 18618.[PubMed] [CrossRef]
184. Chuong EB,, Rumi MA,, Soares MJ,, Baker JC . 2013. Endogenous retroviruses function as species-specific enhancer elements in the placenta. Nat Genet 45 : 325 329.[PubMed] [CrossRef]
185. Jacques P-E,, Jeyakani J,, Bourque G . 2013. The majority of primate-specific regulatory sequences are derived from transposable elements. PLoS Genet 9 : e1003504. [PubMed] [CrossRef]
186. Kapusta A,, Kronenberg Z,, Lynch VJ,, Zhuo X,, Ramsay L,, Bourque G,, Yandell M,, Feschotte C . 2013. Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLoS Genet 9 : e1003470. [PubMed] [CrossRef]
187. Kelley D,, Rinn J . 2013. Transposable elements reveal a stem cell specific class of long noncoding RNAs. Genome Biol 13 : R107. [PubMed] [CrossRef]
188. St Laurent G,, Shtokalo D,, Dong B,, Tackett M,, Fan X,, Lazorthes S,, Nicolas E,, Sang N,, Triche T,, McCaffrey T,, Xiao W,, Kapranov P . 2013. VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer. Genome Biol 14 : R73. [PubMed] [CrossRef]
189. Santoni F,, Guerra J,, Luban J . 2012. HERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency. Retrovirology 9 : 111. [PubMed] [CrossRef]
190. Xie W,, Schultz MD,, Lister R,, Hou Z,, Rajagopal N,, Ray P,, Whitaker JW,, Tian S,, Hawkins RD,, Leung D,, Yang H,, Wang T,, Lee AY,, Swanson SA,, Zhang J,, Zhu Y,, Kim A,, Nery JR,, Urich MA,, Kuan S,, Yen C-a,, Klugman S,, Yu P,, Suknuntha K,, Propson NE,, Chen H,, Edsall LE,, Wagner U,, Li Y,, Ye Z,, Kulkarni A,, Xuan Z,, Chung W-Y,, Chi NC,, Antosiewicz-Bourget JE,, Slukvin I,, Stewart R,, Zhang MQ,, Wang W,, Thomson JA,, Ecker JR,, Ren B . 2013. Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153 : 1134 11348.[PubMed] [CrossRef]
191. Fort A,, Hashimoto K,, Yamada D,, Salimullah M,, Keya CA,, Saxena A,, Bonetti A,, Voineagu I,, Bertin N,, Kratz A,, Noro Y,, Wong C-H,, de Hoon M,, Andersson R,, Sandelin A,, Suzuki H,, Wei C-L,, Koseki H,, The FC,, Hasegawa Y,, Forrest ARR,, Carninci P . 2014. Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nat Genet 46 : 558 566.[PubMed] [CrossRef]
192. Loewer S,, Cabili MN,, Guttman M,, Loh Y-H,, Thomas K,, Park IH,, Garber M,, Curran M,, Onder T,, Agarwal S,, Manos PD,, Datta S,, Lander ES,, Schlaeger TM,, Daley GQ,, Rinn JL . 2010. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 42 : 1113 1117.[PubMed] [CrossRef]
193. Lu X,, Sachs F,, Ramsay L,, Jacques PE,, Goke J,, Bourque G,, Ng HH . 2014. The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nat Struct Mol Biol 21 : 423 425.[PubMed] [CrossRef]
194. Wang Y,, Xu Z,, Jiang J,, Xu C,, Kang J,, Xiao L,, Wu M,, Xiong J,, Guo X,, Liu H . 2013. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25 : 69 80.[PubMed] [CrossRef]
195. Herquel B,, Ouararhni K,, Martianov I,, Le Gras S,, Ye T,, Keime C,, Lerouge T,, Jost B,, Cammas F,, Losson R,, Davidson I . 2013. Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA. Nat Struct Mol Biol 20 : 339 346.[PubMed] [CrossRef]
196. Emerman M,, Malik HS . 2010. Paleovirology--modern consequences of ancient viruses. PLoS Biol 8 : e1000301. [PubMed] [CrossRef]
197. Dupressoir A,, Marceau G,, Vernochet C,, Benit L,, Kanellopoulos C,, Sapin V,, Heidmann T . 2005. Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae . Proc Natl Sci Adad U S A 102 : 725 730.[PubMed] [CrossRef]
198. Heidmann O,, Vernochet C,, Dupressoir A,, Heidmann T . 2009. Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: a new “syncytin” in a third order of mammals. Retrovirology 6 : 107. [PubMed] [CrossRef]
199. Cornelis