Skip to main content
SpringerLink
Log in

Endogenous Retroviruses and the Epigenome

  • Chapter
  • First Online:
Viruses: Essential Agents of Life

Abstract

Endogenous retroviruses (ERVs) are the evolutionary remnants of ­retroviral germline infections, which are no longer capable of intercellular infectivity. Despite being confined within the genomes of their hosts, ERVs are able to replicate and spread via retrotransposition. This replicative process helps to ensure the elements’ proliferation and long term evolutionary success, but it also imposes a substantial mutational burden on their host genomes. Accordingly, host organisms have evolved a variety of mechanisms to repress ERV transposition, including epigenetic mechanisms based on the modification of chromatin. In particular, DNA methylation and histone modifications are used to silence ERV transcription thereby mitigating their ability cause mutations via transposition. It has recently become apparent that epigenetic and chromatin based regulation of ERVs can also exert substantial regulatory effects on host genes. In this chapter, we provide a number of examples illustrating how chromatin modifications of ERV insertions relate to host gene regulation including both deleterious cases as well as exapted cases whereby epigenetically activated ERV elements provide functional utility to their host genomes via the provisioning of novel regulatory sequences. For example, we discuss ERV-derived promoter and enhancer sequences in the human genome that are epigenetically modified in a cell-type specific manner to help drive differential expression of host genes. The genomic abundance of ERVs, taken together with their proximity to host genes and their propensity to be epigenetically modified, suggest that this kind of phenomenon may be far more common than previously imagined. Furthermore, the environmental responsiveness of epigenetic pathways suggests the possibility that ERVs, along with other classes of epigenetically modified TEs, may serve to coordinately modify host gene regulatory programs in response to environmental challenges.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, Weng Z et al (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447(7146):799–816. doi:10.1038/nature05874

    Article  PubMed  CAS  Google Scholar 

  • Brosius J, Gould SJ (1992) On “genomenclature”: a comprehensive (and respectful) taxonomy for pseudogenes and other “junk DNA”. Proc Natl Acad Sci USA 89(22):10706–10710

    Article  PubMed  CAS  Google Scholar 

  • Cohen CJ, Rebollo R, Babovic S, Dai EL, Robinson WP, Mager DL (2011) Placenta-specific expression of the interleukin-2 (IL-2) receptor beta subunit from an endogenous retroviral promoter. J Biol Chem 286(41):35543–35552. doi:10.1074/jbc.M111.227637

    Article  PubMed  CAS  Google Scholar 

  • Conley AB, Piriyapongsa J, Jordan IK (2008) Retroviral promoters in the human genome. Bioinformatics 24(14):1563–1567. doi:btn243%20[pii]%2010.1093/bioinformatics/btn243

    Article  PubMed  CAS  Google Scholar 

  • Cropley JE, Suter CM, Beckman KB, Martin DI (2006) Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proc Natl Acad Sci USA 103(46):17308–17312. doi:10.1073/pnas.0607090103

    Article  PubMed  CAS  Google Scholar 

  • Doolittle RF, Feng DF, Johnson MS, McClure MA (1989) Origins and evolutionary relationships of retroviruses. Q Rev Biol 64(1):1–30

    Article  PubMed  CAS  Google Scholar 

  • Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X et al (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473(7345):43–49. doi:10.1038/nature09906

    Article  PubMed  CAS  Google Scholar 

  • Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, Schroder K et al (2009) The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41(5):563–571. doi:10.1038/ng.368

    Article  PubMed  CAS  Google Scholar 

  • Feil R, Fraga MF (2011) Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 13(2):97–109. doi:10.1038/nrg3142

    Google Scholar 

  • Gould SJ, Vrba ES (1982) Exaptation-a missing term in the science of form. Paleobiol 8:4–15

    Google Scholar 

  • Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39(3):311–318. doi:10.1038/ng1966

    Article  PubMed  CAS  Google Scholar 

  • Hollister JD, Gaut BS (2009) Epigenetic silencing of transposable elements: a trade-off between reduced transposition and deleterious effects on neighboring gene expression. Genome Res 19(8):1419–1428. doi:10.1101/gr.091678.109

    Article  PubMed  CAS  Google Scholar 

  • Huda A, Marino-Ramirez L, Jordan IK (2010) Epigenetic histone modifications of human transposable elements: genome defense versus exaptation. Mobile DNA 1(1):2. doi:10.1186/1759-8753-1-2

    Article  PubMed  Google Scholar 

  • Huda A, Bowen NJ, Conley AB, Jordan IK (2011a) Epigenetic regulation of transposable element derived human gene promoters. Gene 475(1):39–48. doi:S0378-1119(10)00476-2 [pii] 10.1016/j.gene.2010.12.010

    Article  PubMed  CAS  Google Scholar 

  • Huda A, Tyagi E, Marino-Ramirez L, Bowen NJ, Jjingo D, Jordan IK (2011b) Prediction of transposable element derived enhancers using chromatin modification profiles. PLoS One 6(11):e27513. doi:10.1371/journal.pone.0027513

    Article  PubMed  CAS  Google Scholar 

  • Jordan IK, Rogozin IB, Glazko GV, Koonin EV (2003) Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet 19(2):68–72

    Article  PubMed  CAS  Google Scholar 

  • Kodzius R, Kojima M, Nishiyori H, Nakamura M, Fukuda S, Tagami M, Sasaki D et al (2006) CAGE: cap analysis of gene expression. Nat Methods 3(3):211–222. doi:10.1038/nmeth0306-211

    Article  PubMed  CAS  Google Scholar 

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921. doi:10.1038/35057062

    Article  PubMed  CAS  Google Scholar 

  • Leung DC, Lorincz MC (2011) Silencing of endogenous retroviruses: when and why do histone marks predominate? Trends Biochem Sci. doi:10.1016/j.tibs.2011.11.006

  • Levin HL, Moran JV (2011) Dynamic interactions between transposable elements and their hosts. Nat Rev Genet 12(9):615–627. doi:10.1038/nrg3030

    Article  PubMed  CAS  Google Scholar 

  • Li J, Akagi K, Hu Y, Trivett AL, Hlynialuk CJ, Swing DA, Volfovsky N et al (2012) Mouse endogenous retroviruses can trigger premature transcriptional termination at a distance. Genome Res. doi:10.1101/gr.130740.111

  • Lippman Z, Gendrel AV, Black M, Vaughn MW, Dedhia N, McCombie WR, Lavine K et al (2004) Role of transposable elements in heterochromatin and epigenetic control. Nature 430(6998):471–476. doi:10.1038/nature02651

    Article  PubMed  CAS  Google Scholar 

  • Lower R, Lower J, Kurth R (1996) The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc Natl Acad Sci USA 93(11):5177–5184

    Article  PubMed  CAS  Google Scholar 

  • 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(1):e2. doi:10.1371/journal.pgen.0020002

    Article  PubMed  Google Scholar 

  • Marino-Ramirez L, Jordan IK (2006) Transposable element derived DNaseI-hypersensitive sites in the human genome. Biol Direct 1:20. doi:10.1186/1745-6150-1-20

    Article  PubMed  Google Scholar 

  • Martens JH, O’Sullivan RJ, Braunschweig U, Opravil S, Radolf M, Steinlein P, Jenuwein T (2005) The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J 24(4):800–812. doi:10.1038/sj.emboj.7600545

    Article  PubMed  CAS  Google Scholar 

  • McClintock B (1948) Mutable loci in maize. Carnegie Inst Wash Year B 47:155–169

    Google Scholar 

  • McClintock B (1984) The significance of responses of the genome to challenge. Science 226(4676):792–801

    Article  PubMed  CAS  Google Scholar 

  • Michaud EJ, van Vugt MJ, Bultman SJ, Sweet HO, Davisson MT, Woychik RP (1994) Differential expression of a new dominant agouti allele (Aiapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev 8(12):1463–1472

    Article  PubMed  CAS  Google Scholar 

  • Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153):553–560. doi:10.1038/nature06008

    Article  PubMed  CAS  Google Scholar 

  • Morgan HD, Sutherland HG, Martin DI, Whitelaw E (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23(3):314–318. doi:10.1038/15490

    Article  PubMed  CAS  Google Scholar 

  • Ng P, Wei CL, Sung WK, Chiu KP, Lipovich L, Ang CC, Gupta S et al (2005) Gene identification signature (GIS) analysis for transcriptome characterization and genome annotation. Nat Methods 2(2):105–111. doi:10.1038/nmeth733

    Article  PubMed  CAS  Google Scholar 

  • 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(4):597–606. doi:10.1016/j.devcel.2004.09.004

    Article  PubMed  CAS  Google Scholar 

  • Rebollo R, Karimi MM, Bilenky M, Gagnier L, Miceli-Royer K, Zhang Y, Goyal P et al (2011) Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms. PLoS Genet 7(9):e1002301. doi:10.1371/journal.pgen.1002301

    Article  PubMed  CAS  Google Scholar 

  • Robertson G, Hirst M, Bainbridge M, Bilenky M, Zhao Y, Zeng T, Euskirchen G et al (2007) Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing. Nat Methods 4(8):651–657. doi:10.1038/nmeth1068

    Article  PubMed  CAS  Google Scholar 

  • Rosenbloom KR, Dreszer TR, Pheasant M, Barber GP, Meyer LR, Pohl A, Raney BJ et al (2010) ENCODE whole-genome data in the UCSC Genome Browser. Nucleic Acids Res 38 (Database issue):D620–625. doi:10.1093/nar/gkp961

  • Sasaki T, Nishihara H, Hirakawa M, Fujimura K, Tanaka M, Kokubo N, Kimura-Yoshida C et al (2008) Possible involvement of SINEs in mammalian-specific brain formation. Proc Natl Acad Sci USA 105(11):4220–4225. doi:10.1073/pnas.0709398105

    Article  PubMed  CAS  Google Scholar 

  • van de Lagemaat LN, Landry JR, Mager DL, Medstrand P (2003) Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet 19(10):530–536

    Article  PubMed  Google Scholar 

  • Visel A, Blow MJ, Li Z, Zhang T, Akiyama JA, Holt A, Plajzer-Frick I et al (2009) ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457(7231):854–858. doi:10.1038/nature07730

    Article  PubMed  CAS  Google Scholar 

  • Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420(6915):520–562. doi:10.1038/nature01262

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Zhou T, He J, Mountz JD (1993) Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene. J Exp Med 178(2):461–468

    Article  PubMed  CAS  Google Scholar 

  • Xiong Y, Eickbush TH (1988) Similarity of reverse transcriptase-like sequences of viruses, ­transposable elements, and mitochondrial introns. Mol Biol Evol 5(6):675–690

    PubMed  CAS  Google Scholar 

  • Xiong Y, Eickbush TH (1990) Origin and evolution of retroelements based upon their reverse transcriptase sequences. EMBO J 9(10):3353–3362

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA, 30332, USA

    Andrew B. Conley & I. King Jordan

  2. PanAmerican Bioinformatics Institute, Santa Marta, Magdalena, Colombia

    I. King Jordan

Authors
  1. Andrew B. Conley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. King Jordan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. King Jordan .

Editor information

Editors and Affiliations

  1. Telos - Philosophische Praxis, Vogelsangstr. 18c, BĂĽrmoos, 5111, Austria

    GĂĽnther Witzany

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Conley, A.B., Jordan, I.K. (2012). Endogenous Retroviruses and the Epigenome. In: Witzany, G. (eds) Viruses: Essential Agents of Life. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4899-6_16

Download citation

Publish with us

Policies and ethics

Search

Navigation