Transcription of Endogenous Retroviruses: Broad and Precise Mechanisms of Control
Abstract
:1. Introduction
2. Endogenous Retroviruses
3. Nomenclature and General Properties of ERVs
3.1. ERV Nomenclature
3.2. General Properties and Recent Findings of Select ERV Groups
4. Regulatory Features of ERVs
4.1. ERV LTRs Are Enriched in Transcription Factor Binding Sites
4.2. LTRs Provide a Source of Modularity to Gene Regulation
4.3. ERVs Are Regulated by Epigenetic Control
4.4. ERV Silencing Mechanisms Are Reversible
5. ERVs Are Derepressed in Abnormal Cellular States
5.1. ERV Expression Is Associated with Human Disease
5.2. ERVs Are Broadly Expressed in Various Cell Types
5.3. The Cancer ERV Transcriptome Is Limited but Complex
5.4. ERVs Induce a State of ‘Viral Mimicry’
5.5. ERVs Expressed in Cancers Include Ones Exapted in Development
6. ERV Expression in Embryogenesis Is Precisely Regulated
6.1. Mouse ERV-L
6.2. Human ERV-L
6.3. Human ERV-H
6.4. Human ERV-K
6.5. The Evolution of DUX Incorporates Species-Specific ERV Activation
7. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Wells, J.N.; Feschotte, C. A Field Guide to Eukaryotic Transposable Elements. Annu. Rev. Genet. 2020, 54, 539–561. [Google Scholar] [CrossRef]
- Johnson, W.E. Origins and evolutionary consequences of ancient endogenous retroviruses. Nat. Rev. Microbiol. 2019, 17, 355–370. [Google Scholar] [CrossRef] [PubMed]
- Geis, F.K.; Goff, S.P. Silencing and Transcriptional Regulation of Endogenous Retroviruses: An Overview. Viruses 2020, 12, 884. [Google Scholar] [CrossRef]
- Chuong, E.B.; Elde, N.C.; Feschotte, C. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 2016, 351, 1083–1087. [Google Scholar] [CrossRef] [PubMed]
- Chuong, E.B.; Elde, N.C.; Feschotte, C. Regulatory activities of transposable elements: From conflicts to benefits. Nat. Rev. Genet. 2017, 18, 71–86. [Google Scholar] [CrossRef]
- Babaian, A.; Mager, D.L. Endogenous retroviral promoter exaptation in human cancer. Mob. DNA 2016, 7, 24. [Google Scholar] [CrossRef]
- Kitsou, K.; Lagiou, P.; Magiorkinis, G. Human endogenous retroviruses in cancer: Oncogenesis mechanisms and clinical implications. J. Med. Virol. 2023, 95, e28350. [Google Scholar] [CrossRef] [PubMed]
- Aiewsakun, P.; Katzourakis, A. Marine origin of retroviruses in the early Palaeozoic Era. Nat. Commun. 2017, 8, 13954. [Google Scholar] [CrossRef]
- Anai, Y.; Ochi, H.; Watanabe, S.; Nakagawa, S.; Kawamura, M.; Gojobori, T.; Nishigaki, K. Infectious endogenous retroviruses in cats and emergence of recombinant viruses. J. Virol. 2012, 86, 8634–8644. [Google Scholar] [CrossRef] [PubMed]
- Hayward, A.; Cornwallis, C.K.; Jern, P. Pan-vertebrate comparative genomics unmasks retrovirus macroevolution. Proc. Natl. Acad. Sci. USA 2015, 112, 464–469. [Google Scholar] [CrossRef]
- Katzourakis, A.; Gifford, R.J.; Tristem, M.; Gilbert, M.T.; Pybus, O.G. Macroevolution of complex retroviruses. Science 2009, 325, 1512. [Google Scholar] [CrossRef]
- Brown, P.O. Integration. In Retroviruses; Coffin, J.M., Hughes, S.H., Varmus, H., Eds.; Cold Spring Harbor Laboratory Press: Plainview, NY, USA, 1997; p. xv. 843p. [Google Scholar]
- Jern, P.; Coffin, J.M. Effects of retroviruses on host genome function. Annu. Rev. Genet. 2008, 42, 709–732. [Google Scholar] [CrossRef] [PubMed]
- Vogt, V.M. Retroviral Virions and Genomes. In Retroviruses; Coffin, J.M., Hughes, S.H., Varmus, H., Eds.; Cold Spring Harbor Laboratory Press: Plainview, NY, USA, 1997; p. xv. 843p. [Google Scholar]
- Stoye, J.P. Studies of endogenous retroviruses reveal a continuing evolutionary saga. Nat. Rev. Microbiol. 2012, 10, 395–406. [Google Scholar] [CrossRef] [PubMed]
- Ngo, M.H.; Arnal, M.; Sumi, R.; Kawasaki, J.; Miyake, A.; Grant, C.K.; Otoi, T.; Fernandez de Luco, D.; Nishigaki, K. Tracking the Fate of Endogenous Retrovirus Segregation in Wild and Domestic Cats. J. Virol. 2019, 93, e01324. [Google Scholar] [CrossRef] [PubMed]
- Shimode, S.; Nakagawa, S.; Miyazawa, T. Multiple invasions of an infectious retrovirus in cat genomes. Sci. Rep. 2015, 5, 8164. [Google Scholar] [CrossRef] [PubMed]
- Halo, J.V.; Pendleton, A.L.; Jarosz, A.S.; Gifford, R.J.; Day, M.L.; Kidd, J.M. Origin and recent expansion of an endogenous gammaretroviral lineage in domestic and wild canids. Retrovirology 2019, 16, 6. [Google Scholar] [CrossRef] [PubMed]
- Jarosz, A.S.; Pendleton, A.L.; Lashbrook, M.J.; Cech, E.; Altieri, M.; Kunch, A.; Modiano, J.F.; Halo, J.V. Expression and high levels of insertional polymorphism of an endogenous gammaretrovirus lineage in dogs. PLoS Genet. 2023, 19, e1011083. [Google Scholar] [CrossRef]
- Fabryova, H.; Hron, T.; Kabickova, H.; Poss, M.; Elleder, D. Induction and characterization of a replication competent cervid endogenous gammaretrovirus (CrERV) from mule deer cells. Virology 2015, 485, 96–103. [Google Scholar] [CrossRef] [PubMed]
- Yang, L.; Malhotra, R.; Chikhi, R.; Elleder, D.; Kaiser, T.; Rong, J.; Medvedev, P.; Poss, M. Recombination Marks the Evolutionary Dynamics of a Recently Endogenized Retrovirus. Mol. Biol. Evol. 2021, 38, 5423–5436. [Google Scholar] [CrossRef]
- Tang, L.; Swedlund, B.; Dupont, S.; Harland, C.; Costa Monteiro Moreira, G.; Durkin, K.; Artesi, M.; Mullaart, E.; Sartelet, A.; Karim, L.; et al. GWAS reveals determinants of mobilization rate and dynamics of an active endogenous retrovirus of cattle. Nat. Commun. 2024, 15, 2154. [Google Scholar] [CrossRef]
- Blyton, M.D.J.; Young, P.R.; Moore, B.D.; Chappell, K.J. Geographic patterns of koala retrovirus genetic diversity, endogenization, and subtype distributions. Proc. Natl. Acad. Sci. USA 2022, 119, e2122680119. [Google Scholar] [CrossRef] [PubMed]
- Lillie, M.; Pettersson, M.; Jern, P. Contrasting segregation patterns among endogenous retroviruses across the koala population. Commun. Biol. 2024, 7, 350. [Google Scholar] [CrossRef] [PubMed]
- Jern, P.; Greenwood, A.D. Wildlife endogenous retroviruses: Colonization, consequences, and cooption. Trends Genet. 2024, 40, 149–159. [Google Scholar] [CrossRef] [PubMed]
- Hughes, J.F.; Coffin, J.M. Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: Implications for human and viral evolution. Proc. Natl. Acad. Sci. USA 2004, 101, 1668–1672. [Google Scholar] [CrossRef] [PubMed]
- Belshaw, R.; Watson, J.; Katzourakis, A.; Howe, A.; Woolven-Allen, J.; Burt, A.; Tristem, M. Rate of recombinational deletion among human endogenous retroviruses. J. Virol. 2007, 81, 9437–9442. [Google Scholar] [CrossRef] [PubMed]
- Thomas, J.; Perron, H.; Feschotte, C. Variation in proviral content among human genomes mediated by LTR recombination. Mob. DNA 2018, 9, 36. [Google Scholar] [CrossRef] [PubMed]
- Thompson, P.J.; Macfarlan, T.S.; Lorincz, M.C. Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire. Mol. Cell 2016, 62, 766–776. [Google Scholar] [CrossRef]
- Gemmell, P.; Hein, J.; Katzourakis, A. Orthologous endogenous retroviruses exhibit directional selection since the chimp-human split. Retrovirology 2015, 12, 52. [Google Scholar] [CrossRef] [PubMed]
- Gemmell, P.; Hein, J.; Katzourakis, A. Phylogenetic Analysis Reveals That ERVs “Die Young” but HERV-H Is Unusually Conserved. PLoS Comput. Biol. 2016, 12, e1004964. [Google Scholar] [CrossRef]
- Gemmell, P.; Hein, J.; Katzourakis, A. The Exaptation of HERV-H: Evolutionary Analyses Reveal the Genomic Features of Highly Transcribed Elements. Front. Immunol. 2019, 10, 1339. [Google Scholar] [CrossRef]
- Izsvak, Z.; Wang, J.; Singh, M.; Mager, D.L.; Hurst, L.D. Pluripotency and the endogenous retrovirus HERVH: Conflict or serendipity? Bioessays 2016, 38, 109–117. [Google Scholar] [CrossRef] [PubMed]
- Hughes, J.F.; Coffin, J.M. Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat. Genet. 2001, 29, 487–489. [Google Scholar] [CrossRef] [PubMed]
- Gu, W.; Zhang, F.; Lupski, J.R. Mechanisms for human genomic rearrangements. Pathogenetics 2008, 1, 4. [Google Scholar] [CrossRef]
- Hughes, J.F.; Coffin, J.M. Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome. Genetics 2005, 171, 1183–1194. [Google Scholar] [CrossRef]
- Trombetta, B.; Fantini, G.; D’Atanasio, E.; Sellitto, D.; Cruciani, F. Evidence of extensive non-allelic gene conversion among LTR elements in the human genome. Sci. Rep. 2016, 6, 28710. [Google Scholar] [CrossRef]
- Kjeldbjerg, A.L.; Villesen, P.; Aagaard, L.; Pedersen, F.S. Gene conversion and purifying selection of a placenta-specific ERV-V envelope gene during simian evolution. BMC Evol. Biol. 2008, 8, 266. [Google Scholar] [CrossRef]
- Boso, G.; Fleck, K.; Carley, S.; Liu, Q.; Buckler-White, A.; Kozak, C.A. The Oldest Co-opted gag Gene of a Human Endogenous Retrovirus Shows Placenta-Specific Expression and Is Upregulated in Diffuse Large B-Cell Lymphomas. Mol. Biol. Evol. 2021, 38, 5453–5471. [Google Scholar] [CrossRef] [PubMed]
- Mouse Genome Sequencing, C.; Waterston, R.H.; Lindblad-Toh, K.; Birney, E.; Rogers, J.; Abril, J.F.; Agarwal, P.; Agarwala, R.; Ainscough, R.; Alexandersson, M.; et al. Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420, 520–562. [Google Scholar] [CrossRef] [PubMed]
- Venter, J.C.; Adams, M.D.; Myers, E.W.; Li, P.W.; Mural, R.J.; Sutton, G.G.; Smith, H.O.; Yandell, M.; Evans, C.A.; Holt, R.A.; et al. The sequence of the human genome. Science 2001, 291, 1304–1351. [Google Scholar] [CrossRef]
- Lindblad-Toh, K.; Wade, C.M.; Mikkelsen, T.S.; Karlsson, E.K.; Jaffe, D.B.; Kamal, M.; Clamp, M.; Chang, J.L.; Kulbokas, E.J., 3rd; Zody, M.C.; et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 2005, 438, 803–819. [Google Scholar] [CrossRef]
- Pontius, J.U.; Mullikin, J.C.; Smith, D.R.; Agencourt Sequencing, T.; Lindblad-Toh, K.; Gnerre, S.; Clamp, M.; Chang, J.; Stephens, R.; Neelam, B.; et al. Initial sequence and comparative analysis of the cat genome. Genome Res. 2007, 17, 1675–1689. [Google Scholar] [CrossRef] [PubMed]
- Nelson, P.N.; Carnegie, P.R.; Martin, J.; Davari Ejtehadi, H.; Hooley, P.; Roden, D.; Rowland-Jones, S.; Warren, P.; Astley, J.; Murray, P.G. Demystified. Human endogenous retroviruses. Mol. Pathol. 2003, 56, 11–18. [Google Scholar] [CrossRef] [PubMed]
- Boeke, J.D.; Stoye, J.P. Retrotransposons, endogenous retroviruses, and the evolution of retroelements. In Retroviruses; Coffin, J., Hughes, S., Varmus, H., Eds.; CSHL Press: New York, NY, USA, 1997; pp. 343–435. [Google Scholar]
- Meyer, T.J.; Rosenkrantz, J.L.; Carbone, L.; Chavez, S.L. Endogenous Retroviruses: With Us and against Us. Front. Chem. 2017, 5, 23. [Google Scholar] [CrossRef] [PubMed]
- Gifford, R.J.; Blomberg, J.; Coffin, J.M.; Fan, H.; Heidmann, T.; Mayer, J.; Stoye, J.; Tristem, M.; Johnson, W.E. Nomenclature for endogenous retrovirus (ERV) loci. Retrovirology 2018, 15, 59. [Google Scholar] [CrossRef] [PubMed]
- Krupovic, M.; Blomberg, J.; Coffin, J.M.; Dasgupta, I.; Fan, H.; Geering, A.D.; Gifford, R.; Harrach, B.; Hull, R.; Johnson, W.; et al. Ortervirales: New Virus Order Unifying Five Families of Reverse-Transcribing Viruses. J. Virol. 2018, 92, e00515. [Google Scholar] [CrossRef] [PubMed]
- Coffin, J.; Blomberg, J.; Fan, H.; Gifford, R.; Hatziioannou, T.; Lindemann, D.; Mayer, J.; Stoye, J.; Tristem, M.; Johnson, W.; et al. ICTV Virus Taxonomy Profile: Retroviridae 2021. J. Gen. Virol. 2021, 102, 001712. [Google Scholar] [CrossRef] [PubMed]
- Johnson, W.E. Endogenous Retroviruses in the Genomics Era. Annu. Rev. Virol. 2015, 2, 135–159. [Google Scholar] [CrossRef] [PubMed]
- Kojima, K.K. Human transposable elements in Repbase: Genomic footprints from fish to humans. Mob. DNA 2018, 9, 2. [Google Scholar] [CrossRef] [PubMed]
- Vargiu, L.; Rodriguez-Tome, P.; Sperber, G.O.; Cadeddu, M.; Grandi, N.; Blikstad, V.; Tramontano, E.; Blomberg, J. Classification and characterization of human endogenous retroviruses; mosaic forms are common. Retrovirology 2016, 13, 7. [Google Scholar] [CrossRef]
- Grandi, N.; Cadeddu, M.; Blomberg, J.; Tramontano, E. Contribution of type W human endogenous retroviruses to the human genome: Characterization of HERV-W proviral insertions and processed pseudogenes. Retrovirology 2016, 13, 67. [Google Scholar] [CrossRef]
- Subramanian, R.P.; Wildschutte, J.H.; Russo, C.; Coffin, J.M. Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses. Retrovirology 2011, 8, 90. [Google Scholar] [CrossRef]
- Benit, L.; Lallemand, J.B.; Casella, J.F.; Philippe, H.; Heidmann, T. ERV-L elements: A family of endogenous retrovirus-like elements active throughout the evolution of mammals. J. Virol. 1999, 73, 3301–3308. [Google Scholar] [CrossRef]
- Costas, J. Molecular characterization of the recent intragenomic spread of the murine endogenous retrovirus MuERV-L. J. Mol. Evol. 2003, 56, 181–186. [Google Scholar] [CrossRef]
- Franke, V.; Ganesh, S.; Karlic, R.; Malik, R.; Pasulka, J.; Horvat, F.; Kuzman, M.; Fulka, H.; Cernohorska, M.; Urbanova, J.; et al. Long terminal repeats power evolution of genes and gene expression programs in mammalian oocytes and zygotes. Genome Res. 2017, 27, 1384–1394. [Google Scholar] [CrossRef]
- Zuo, Z. The successive emergence of ERVL-MaLRs in primates. Virus Evol. 2023, 9, vead072. [Google Scholar] [CrossRef]
- Magiorkinis, G.; Belshaw, R.; Katzourakis, A. ‘There and back again’: Revisiting the pathophysiological roles of human endogenous retroviruses in the post-genomic era. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2013, 368, 20120504. [Google Scholar] [CrossRef]
- Young, J.M.; Whiddon, J.L.; Yao, Z.; Kasinathan, B.; Snider, L.; Geng, L.N.; Balog, J.; Tawil, R.; van der Maarel, S.M.; Tapscott, S.J. DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis. PLoS Genet. 2013, 9, e1003947. [Google Scholar] [CrossRef]
- Shi, M.; Chen, F.; Sahu, S.K.; Wang, Q.; Yang, S.; Wang, Z.; Chen, J.; Liu, H.; Hou, Z.; Fang, S.G.; et al. Haplotype-resolved chromosome-scale genomes of the Asian and African Savannah Elephants. Sci. Data 2024, 11, 63. [Google Scholar] [CrossRef]
- Springer, M.S.; Murphy, W.J.; Eizirik, E.; O’Brien, S.J. Placental mammal diversification and the Cretaceous-Tertiary boundary. Proc. Natl. Acad. Sci. USA 2003, 100, 1056–1061. [Google Scholar] [CrossRef]
- Lavie, L.; Medstrand, P.; Schempp, W.; Meese, E.; Mayer, J. Human endogenous retrovirus family HERV-K(HML-5): Status, evolution, and reconstruction of an ancient betaretrovirus in the human genome. J. Virol. 2004, 78, 8788–8798. [Google Scholar] [CrossRef]
- Wildschutte, J.H.; Williams, Z.H.; Montesion, M.; Subramanian, R.P.; Kidd, J.M.; Coffin, J.M. Discovery of unfixed endogenous retrovirus insertions in diverse human populations. Proc. Natl. Acad. Sci. USA 2016, 113, E2326–E2334. [Google Scholar] [CrossRef]
- Macfarlane, C.M.; Badge, R.M. Genome-wide amplification of proviral sequences reveals new polymorphic HERV-K(HML-2) proviruses in humans and chimpanzees that are absent from genome assemblies. Retrovirology 2015, 12, 35. [Google Scholar] [CrossRef] [PubMed]
- Holloway, J.R.; Williams, Z.H.; Freeman, M.M.; Bulow, U.; Coffin, J.M. Gorillas have been infected with the HERV-K (HML-2) endogenous retrovirus much more recently than humans and chimpanzees. Proc. Natl. Acad. Sci. USA 2019, 116, 1337–1346. [Google Scholar] [CrossRef]
- Turner, G.; Barbulescu, M.; Su, M.; Jensen-Seaman, M.I.; Kidd, K.K.; Lenz, J. Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr. Biol. 2001, 11, 1531–1535. [Google Scholar] [CrossRef]
- Dewannieux, M.; Harper, F.; Richaud, A.; Letzelter, C.; Ribet, D.; Pierron, G.; Heidmann, T. Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res. 2006, 16, 1548–1556. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.N.; Bieniasz, P.D. Reconstitution of an infectious human endogenous retrovirus. PLoS Pathog. 2007, 3, e10. [Google Scholar] [CrossRef]
- Goodchild, N.L.; Wilkinson, D.A.; Mager, D.L. Recent evolutionary expansion of a subfamily of RTVL-H human endogenous retrovirus-like elements. Virology 1993, 196, 778–788. [Google Scholar] [CrossRef]
- Jern, P. Genomic Variation and Evolution of HERV-H and Other Endogenous Retroviruses (ERVs). Ph.D. Thesis, Uppsala Universitet, Uppsala, Sweden, 2005; p. 77. [Google Scholar]
- Carter, T.A.; Singh, M.; Dumbovic, G.; Chobirko, J.D.; Rinn, J.L.; Feschotte, C. Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo. Elife 2022, 11, e76257. [Google Scholar] [CrossRef] [PubMed]
- Costas, J. Characterization of the intragenomic spread of the human endogenous retrovirus family HERV-W. Mol. Biol. Evol. 2002, 19, 526–533. [Google Scholar] [CrossRef]
- Perron, H.; Garson, J.A.; Bedin, F.; Beseme, F.; Paranhos-Baccala, G.; Komurian-Pradel, F.; Mallet, F.; Tuke, P.W.; Voisset, C.; Blond, J.L.; et al. Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The Collaborative Research Group on Multiple Sclerosis. Proc. Natl. Acad. Sci. USA 1997, 94, 7583–7588. [Google Scholar] [CrossRef]
- Perron, H.; Hamdani, N.; Faucard, R.; Lajnef, M.; Jamain, S.; Daban-Huard, C.; Sarrazin, S.; LeGuen, E.; Houenou, J.; Delavest, M.; et al. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder. Transl. Psychiatry 2012, 2, e201. [Google Scholar] [CrossRef]
- Dupressoir, A.; Lavialle, C.; Heidmann, T. From ancestral infectious retroviruses to bona fide cellular genes: Role of the captured syncytins in placentation. Placenta 2012, 33, 663–671. [Google Scholar] [CrossRef]
- Imakawa, K.; Kusama, K.; Kaneko-Ishino, T.; Nakagawa, S.; Kitao, K.; Miyazawa, T.; Ishino, F. Endogenous Retroviruses and Placental Evolution, Development, and Diversity. Cells 2022, 11, 2458. [Google Scholar] [CrossRef] [PubMed]
- Sinha, A.; Johnson, W.E. Retroviruses of the RDR superinfection interference group: Ancient origins and broad host distribution of a promiscuous Env gene. Curr. Opin. Virol. 2017, 25, 105–112. [Google Scholar] [CrossRef] [PubMed]
- Kang, B.K.; Jung, Y.T. A Replication-Competent Retroviral Vector Expressing the HERV-W Envelope Glycoprotein is a Potential Tool for Cancer Gene Therapy. J. Microbiol. Biotechnol. 2024, 34, 280–288. [Google Scholar] [CrossRef]
- Kitao, K.; Nakagawa, S.; Miyazawa, T. An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation. Retrovirology 2021, 18, 36. [Google Scholar] [CrossRef]
- Fort, V.; Khelifi, G.; Hussein, S.M.I. Long non-coding RNAs and transposable elements: A functional relationship. Biochim. Biophys. Acta Mol. Cell Res. 2021, 1868, 118837. [Google Scholar] [CrossRef]
- Gibb, E.A.; Warren, R.L.; Wilson, G.W.; Brown, S.D.; Robertson, G.A.; Morin, G.B.; Holt, R.A. Activation of an endogenous retrovirus-associated long non-coding RNA in human adenocarcinoma. Genome Med. 2015, 7, 22. [Google Scholar] [CrossRef]
- Hu, T.; Pi, W.; Zhu, X.; Yu, M.; Ha, H.; Shi, H.; Choi, J.H.; Tuan, D. Long non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function. Nucleic Acids Res. 2017, 45, 4479–4492. [Google Scholar] [CrossRef]
- Karttunen, K.; Patel, D.; Xia, J.; Fei, L.; Palin, K.; Aaltonen, L.; Sahu, B. Transposable elements as tissue-specific enhancers in cancers of endodermal lineage. Nat. Commun. 2023, 14, 5313. [Google Scholar] [CrossRef]
- Zhou, B.; Qi, F.; Wu, F.; Nie, H.; Song, Y.; Shao, L.; Han, J.; Wu, Z.; Saiyin, H.; Wei, G.; et al. Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression. mBio 2019, 10, e00937. [Google Scholar] [CrossRef]
- Ito, J.; Sugimoto, R.; Nakaoka, H.; Yamada, S.; Kimura, T.; Hayano, T.; Inoue, I. Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses. PLoS Genet. 2017, 13, e1006883. [Google Scholar] [CrossRef]
- Rabson, A.B.; Graves, B.J. Synthesis and Processing of Viral RNA. In Retroviruses; Coffin, J.M., Hughes, S.H., Varmus, H., Eds.; Cold Spring Harbor Laboratory Press: Plainview, NY, USA, 1997; p. xv. 843p. [Google Scholar]
- Benachenhou, F.; Jern, P.; Oja, M.; Sperber, G.; Blikstad, V.; Somervuo, P.; Kaski, S.; Blomberg, J. Evolutionary conservation of orthoretroviral long terminal repeats (LTRs) and ab initio detection of single LTRs in genomic data. PLoS ONE 2009, 4, e5179. [Google Scholar] [CrossRef] [PubMed]
- Benachenhou, F.; Sperber, G.O.; Bongcam-Rudloff, E.; Andersson, G.; Boeke, J.D.; Blomberg, J. Conserved structure and inferred evolutionary history of long terminal repeats (LTRs). Mob. DNA 2013, 4, 5. [Google Scholar] [CrossRef]
- Nikitin, D.; Garazha, A.; Sorokin, M.; Penzar, D.; Tkachev, V.; Markov, A.; Gaifullin, N.; Borger, P.; Poltorak, A.; Buzdin, A. Retroelement-Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution. Cells 2019, 8, 130. [Google Scholar] [CrossRef]
- Zhou, W.; Liang, G.; Molloy, P.L.; Jones, P.A. DNA methylation enables transposable element-driven genome expansion. Proc. Natl. Acad. Sci. USA 2020, 117, 19359–19366. [Google Scholar] [CrossRef]
- Consortium, E.P.; Moore, J.E.; Purcaro, M.J.; Pratt, H.E.; Epstein, C.B.; Shoresh, N.; Adrian, J.; Kawli, T.; Davis, C.A.; Dobin, A.; et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 2020, 583, 699–710. [Google Scholar] [CrossRef] [PubMed]
- Andrews, G.; Fan, K.; Pratt, H.E.; Phalke, N.; Zoonomia Consortium section, s.; Karlsson, E.K.; Lindblad-Toh, K.; Gazal, S.; Moore, J.E.; Weng, Z. Mammalian evolution of human cis-regulatory elements and transcription factor binding sites. Science 2023, 380, eabn7930. [Google Scholar] [CrossRef]
- Montesion, M.; Williams, Z.H.; Subramanian, R.P.; Kuperwasser, C.; Coffin, J.M. Promoter expression of HERV-K (HML-2) provirus-derived sequences is related to LTR sequence variation and polymorphic transcription factor binding sites. Retrovirology 2018, 15, 57. [Google Scholar] [CrossRef]
- Cohen, C.J.; Lock, W.M.; Mager, D.L. Endogenous retroviral LTRs as promoters for human genes: A critical assessment. Gene 2009, 448, 105–114. [Google Scholar] [CrossRef]
- Grandi, N.; Erbi, M.C.; Scognamiglio, S.; Tramontano, E. Human Endogenous Retrovirus (HERV) Transcriptome Is Dynamically Modulated during SARS-CoV-2 Infection and Allows Discrimination of COVID-19 Clinical Stages. Microbiol. Spectr. 2023, 11, e0251622. [Google Scholar] [CrossRef] [PubMed]
- Richardson, S.R.; Doucet, A.J.; Kopera, H.C.; Moldovan, J.B.; Garcia-Perez, J.L.; Moran, J.V. The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes. Microbiol. Spectr. 2015, 3, MDNA3-0061-2014. [Google Scholar] [CrossRef]
- Oomen, M.E.; Torres-Padilla, M.E. Jump-starting life: Balancing transposable element co-option and genome integrity in the developing mammalian embryo. EMBO Rep. 2024, 25, 1721–1733. [Google Scholar] [CrossRef]
- Chuong, E.B.; Rumi, M.A.; Soares, M.J.; Baker, J.C. Endogenous retroviruses function as species-specific enhancer elements in the placenta. Nat. Genet. 2013, 45, 325–329. [Google Scholar] [CrossRef]
- Hansen, T.J.; Fong, S.L.; Day, J.K.; Capra, J.A.; Hodges, E. Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans. Cell Genom. 2024, 4, 100536. [Google Scholar] [CrossRef]
- Hossain, M.J.; Nyame, P.; Monde, K. Species-Specific Transcription Factors Associated with Long Terminal Repeat Promoters of Endogenous Retroviruses: A Comprehensive Review. Biomolecules 2024, 14, 280. [Google Scholar] [CrossRef] [PubMed]
- Jang, H.S.; Shah, N.M.; Du, A.Y.; Dailey, Z.Z.; Pehrsson, E.C.; Godoy, P.M.; Zhang, D.; Li, D.; Xing, X.; Kim, S.; et al. Transposable elements drive widespread expression of oncogenes in human cancers. Nat. Genet. 2019, 51, 611–617. [Google Scholar] [CrossRef]
- Attig, J.; Pape, J.; Doglio, L.; Kazachenka, A.; Ottina, E.; Young, G.R.; Enfield, K.S.; Aramburu, I.V.; Ng, K.W.; Faulkner, N.; et al. Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin. J. Clin. Investig. 2023, 133, e164397. [Google Scholar] [CrossRef]
- Babaian, A.; Romanish, M.T.; Gagnier, L.; Kuo, L.Y.; Karimi, M.M.; Steidl, C.; Mager, D.L. Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. Oncogene 2016, 35, 2542–2546. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.; Ying, Y.; Wang, M.; Chen, Q.; Wang, Y.; Yu, X.; He, W.; Li, J.; Zeng, S.; Xu, C. Comprehensive identification of onco-exaptation events in bladder cancer cell lines revealed L1PA2-SYT1 as a prognosis-relevant event. iScience 2023, 26, 108482. [Google Scholar] [CrossRef]
- Zhang, M.; Zheng, S.; Liang, J.Q. Transcriptional and reverse transcriptional regulation of host genes by human endogenous retroviruses in cancers. Front. Microbiol. 2022, 13, 946296. [Google Scholar] [CrossRef]
- Groger, V.; Emmer, A.; Staege, M.S.; Cynis, H. Endogenous Retroviruses in Nervous System Disorders. Pharmaceuticals 2021, 14, 70. [Google Scholar] [CrossRef]
- Birtle, Z.; Ponting, C.P. Meisetz and the birth of the KRAB motif. Bioinformatics 2006, 22, 2841–2845. [Google Scholar] [CrossRef]
- Helleboid, P.Y.; Heusel, M.; Duc, J.; Piot, C.; Thorball, C.W.; Coluccio, A.; Pontis, J.; Imbeault, M.; Turelli, P.; Aebersold, R.; et al. The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification. EMBO J. 2019, 38, e101220. [Google Scholar] [CrossRef]
- Yang, P.; Wang, Y.; Macfarlan, T.S. The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution. Trends Genet. 2017, 33, 871–881. [Google Scholar] [CrossRef]
- Yang, B.X.; El Farran, C.A.; Guo, H.C.; Yu, T.; Fang, H.T.; Wang, H.F.; Schlesinger, S.; Seah, Y.F.; Goh, G.Y.; Neo, S.P.; et al. Systematic identification of factors for provirus silencing in embryonic stem cells. Cell 2015, 163, 230–245. [Google Scholar] [CrossRef]
- Spencley, A.L.; Bar, S.; Swigut, T.; Flynn, R.A.; Lee, C.H.; Chen, L.F.; Bassik, M.C.; Wysocka, J. Co-transcriptional genome surveillance by HUSH is coupled to termination machinery. Mol. Cell 2023, 83, 1623–1639 e1628. [Google Scholar] [CrossRef]
- Xu, R.; Li, S.; Wu, Q.; Li, C.; Jiang, M.; Guo, L.; Chen, M.; Yang, L.; Dong, X.; Wang, H.; et al. Stage-specific H3K9me3 occupancy ensures retrotransposon silencing in human pre-implantation embryos. Cell Stem Cell 2022, 29, 1051–1066 e1058. [Google Scholar] [CrossRef]
- Ohtani, H.; Liu, M.; Zhou, W.; Liang, G.; Jones, P.A. Switching roles for DNA and histone methylation depend on evolutionary ages of human endogenous retroviruses. Genome Res. 2018, 28, 1147–1157. [Google Scholar] [CrossRef]
- Imbeault, M.; Helleboid, P.Y.; Trono, D. KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks. Nature 2017, 543, 550–554. [Google Scholar] [CrossRef]
- Pontis, J.; Planet, E.; Offner, S.; Turelli, P.; Duc, J.; Coudray, A.; Theunissen, T.W.; Jaenisch, R.; Trono, D. Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs. Cell Stem Cell 2019, 24, 724–735 e725. [Google Scholar] [CrossRef]
- de Tribolet-Hardy, J.; Thorball, C.W.; Forey, R.; Planet, E.; Duc, J.; Coudray, A.; Khubieh, B.; Offner, S.; Pulver, C.; Fellay, J.; et al. Genetic features and genomic targets of human KRAB-zinc finger proteins. Genome Res. 2023, 33, 1409–1423. [Google Scholar] [CrossRef] [PubMed]
- Turelli, P.; Playfoot, C.; Grun, D.; Raclot, C.; Pontis, J.; Coudray, A.; Thorball, C.; Duc, J.; Pankevich, E.V.; Deplancke, B.; et al. Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons. Sci. Adv. 2020, 6, eaba3200. [Google Scholar] [CrossRef]
- Playfoot, C.J.; Duc, J.; Sheppard, S.; Dind, S.; Coudray, A.; Planet, E.; Trono, D. Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain. Genome Res. 2021, 31, 1531–1545. [Google Scholar] [CrossRef]
- Choudhary, M.N.K.; Quaid, K.; Xing, X.; Schmidt, H.; Wang, T. Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes. Nat. Commun. 2023, 14, 634. [Google Scholar] [CrossRef]
- Jansz, N.; Faulkner, G.J. Endogenous retroviruses in the origins and treatment of cancer. Genome Biol. 2021, 22, 147. [Google Scholar] [CrossRef]
- Kassiotis, G. Endogenous retroviruses and the development of cancer. J. Immunol. 2014, 192, 1343–1349. [Google Scholar] [CrossRef] [PubMed]
- Costa, P.; Sales, S.L.A.; Pinheiro, D.P.; Pontes, L.Q.; Maranhao, S.S.; Pessoa, C.D.O.; Furtado, G.P.; Furtado, C.L.M. Epigenetic reprogramming in cancer: From diagnosis to treatment. Front. Cell Dev. Biol. 2023, 11, 1116805. [Google Scholar] [CrossRef]
- Mantovani, F.; Kitsou, K.; Magiorkinis, G. HERVs: Expression Control Mechanisms and Interactions in Diseases and Human Immunodeficiency Virus Infection. Genes 2024, 15, 192. [Google Scholar] [CrossRef]
- Anwar, S.L.; Wulaningsih, W.; Lehmann, U. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation. Int. J. Mol. Sci. 2017, 18, 974. [Google Scholar] [CrossRef]
- Ehrlich, M. DNA hypomethylation in cancer cells. Epigenomics 2009, 1, 239–259. [Google Scholar] [CrossRef] [PubMed]
- Kanholm, T.; Rentia, U.; Hadley, M.; Karlow, J.A.; Cox, O.L.; Diab, N.; Bendall, M.L.; Dawson, T.; McDonald, J.I.; Xie, W.; et al. Oncogenic Transformation Drives DNA Methylation Loss and Transcriptional Activation at Transposable Element Loci. Cancer Res. 2023, 83, 2584–2599. [Google Scholar] [CrossRef]
- Montesion, M.; Bhardwaj, N.; Williams, Z.H.; Kuperwasser, C.; Coffin, J.M. Mechanisms of HERV-K (HML-2) Transcription during Human Mammary Epithelial Cell Transformation. J. Virol. 2018, 92, e01258. [Google Scholar] [CrossRef]
- Patra, S.K. Ras regulation of DNA-methylation and cancer. Exp. Cell Res. 2008, 314, 1193–1201. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Pan, J.; Cong, Y.; Mao, J. Transcriptional Regulation of Endogenous Retroviruses and Their Misregulation in Human Diseases. Int. J. Mol. Sci. 2022, 23, 10112. [Google Scholar] [CrossRef]
- Chen, R.; Ishak, C.A.; De Carvalho, D.D. Endogenous Retroelements and the Viral Mimicry Response in Cancer Therapy and Cellular Homeostasis. Cancer Discov. 2021, 11, 2707–2725. [Google Scholar] [CrossRef]
- Reid Cahn, A.; Bhardwaj, N.; Vabret, N. Dark genome, bright ideas: Recent approaches to harness transposable elements in immunotherapies. Cancer Cell 2022, 40, 792–797. [Google Scholar] [CrossRef]
- Yu, J.; Qiu, P.; Ai, J.; Liu, B.; Han, G.Z.; Zhu, F.; Zhang, W.; Cui, J. Endogenous retrovirus activation: Potential for immunology and clinical applications. Natl. Sci. Rev. 2024, 11, nwae034. [Google Scholar] [CrossRef]
- Weiss, R.A. The search for human RNA tumor viruses. In RNA Tumor Viruses; Weiss, N., Teich, H., Varmus, H.E., Coffin, J., Eds.; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, USA, 1984; pp. 1205–1281. [Google Scholar]
- Callahan, R.; Drohan, W.; Tronick, S.; Schlom, J. Detection and cloning of human DNA sequences related to the mouse mammary tumor virus genome. Proc. Natl. Acad. Sci. USA 1982, 79, 5503–5507. [Google Scholar] [CrossRef]
- Zhang, M.; Liang, J.Q.; Zheng, S. Expressional activation and functional roles of human endogenous retroviruses in cancers. Rev. Med. Virol. 2019, 29, e2025. [Google Scholar] [CrossRef]
- Stricker, E.; Peckham-Gregory, E.C.; Scheurer, M.E. CancerHERVdb: Human Endogenous Retrovirus (HERV) Expression Database for Human Cancer Accelerates Studies of the Retrovirome and Predictions for HERV-Based Therapies. J. Virol. 2023, 97, e0005923. [Google Scholar] [CrossRef]
- Lee, M., Jr.; Ahmad, S.F.; Xu, J. Regulation and function of transposable elements in cancer genomes. Cell. Mol. Life Sci. 2024, 81, 157. [Google Scholar] [CrossRef] [PubMed]
- Liang, B.; Yan, T.; Wei, H.; Zhang, D.; Li, L.; Liu, Z.; Li, W.; Zhang, Y.; Jiang, N.; Meng, Q.; et al. HERVK-mediated regulation of neighboring genes: Implications for breast cancer prognosis. Retrovirology 2024, 21, 4. [Google Scholar] [CrossRef]
- Aftab, A.; Shah, A.A.; Hashmi, A.M. Pathophysiological Role of HERV-W in Schizophrenia. J. Neuropsychiatry Clin. Neurosci. 2016, 28, 17–25. [Google Scholar] [CrossRef] [PubMed]
- Tamouza, R.; Meyer, U.; Foiselle, M.; Richard, J.R.; Wu, C.L.; Boukouaci, W.; Le Corvoisier, P.; Barrau, C.; Lucas, A.; Perron, H.; et al. Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis. Transl. Psychiatry 2021, 11, 377. [Google Scholar] [CrossRef] [PubMed]
- Groger, V.; Cynis, H. Human Endogenous Retroviruses and Their Putative Role in the Development of Autoimmune Disorders Such as Multiple Sclerosis. Front. Microbiol. 2018, 9, 265. [Google Scholar] [CrossRef]
- Kolbe, A.R.; Bendall, M.L.; Pearson, A.T.; Paul, D.; Nixon, D.F.; Perez-Losada, M.; Crandall, K.A. Human Endogenous Retrovirus Expression Is Associated with Head and Neck Cancer and Differential Survival. Viruses 2020, 12, 956. [Google Scholar] [CrossRef]
- Chan, S.M.; Sapir, T.; Park, S.S.; Rual, J.F.; Contreras-Galindo, R.; Reiner, O.; Markovitz, D.M. The HERV-K accessory protein Np9 controls viability and migration of teratocarcinoma cells. PLoS ONE 2019, 14, e0212970. [Google Scholar] [CrossRef]
- Fan, J.; Qin, Z. Roles of Human Endogenous Retrovirus-K-Encoded Np9 in Human Diseases: A Small Protein with Big Functions. Viruses 2024, 16, 581. [Google Scholar] [CrossRef]
- Manca, M.A.; Solinas, T.; Simula, E.R.; Noli, M.; Ruberto, S.; Madonia, M.; Sechi, L.A. HERV-K and HERV-H Env Proteins Induce a Humoral Response in Prostate Cancer Patients. Pathogens 2022, 11, 95. [Google Scholar] [CrossRef]
- Grandi, N.; Tramontano, E. HERV Envelope Proteins: Physiological Role and Pathogenic Potential in Cancer and Autoimmunity. Front. Microbiol. 2018, 9, 462. [Google Scholar] [CrossRef] [PubMed]
- Skandorff, I.; Ragonnaud, E.; Gille, J.; Andersson, A.M.; Schrodel, S.; Duvnjak, L.; Turner, L.; Thirion, C.; Wagner, R.; Holst, P.J. Human Ad19a/64 HERV-W Vaccines Uncover Immunosuppression Domain-Dependent T-Cell Response Differences in Inbred Mice. Int. J. Mol. Sci. 2023, 24, 9972. [Google Scholar] [CrossRef] [PubMed]
- Lemaitre, C.; Tsang, J.; Bireau, C.; Heidmann, T.; Dewannieux, M. A human endogenous retrovirus-derived gene that can contribute to oncogenesis by activating the ERK pathway and inducing migration and invasion. PLoS Pathog. 2017, 13, e1006451. [Google Scholar] [CrossRef] [PubMed]
- Morozov, V.A.; Dao Thi, V.L.; Denner, J. The transmembrane protein of the human endogenous retrovirus--K (HERV-K) modulates cytokine release and gene expression. PLoS ONE 2013, 8, e70399. [Google Scholar] [CrossRef] [PubMed]
- Kremer, D.; Gruchot, J.; Weyers, V.; Oldemeier, L.; Gottle, P.; Healy, L.; Ho Jang, J.; Kang, T.X.Y.; Volsko, C.; Dutta, R.; et al. pHERV-W envelope protein fuels microglial cell-dependent damage of myelinated axons in multiple sclerosis. Proc. Natl. Acad. Sci. USA 2019, 116, 15216–15225. [Google Scholar] [CrossRef] [PubMed]
- Gruchot, J.; Lewen, I.; Dietrich, M.; Reiche, L.; Sindi, M.; Hecker, C.; Herrero, F.; Charvet, B.; Weber-Stadlbauer, U.; Hartung, H.P.; et al. Transgenic expression of the HERV-W envelope protein leads to polarized glial cell populations and a neurodegenerative environment. Proc. Natl. Acad. Sci. USA 2023, 120, e2308187120. [Google Scholar] [CrossRef] [PubMed]
- Dittmar, T.; Hass, R. Intrinsic signalling factors associated with cancer cell-cell fusion. Cell Commun. Signal. 2023, 21, 68. [Google Scholar] [CrossRef] [PubMed]
- Fei, F.; Li, C.; Wang, X.; Du, J.; Liu, K.; Li, B.; Yao, P.; Li, Y.; Zhang, S. Syncytin 1, CD9, and CD47 regulating cell fusion to form PGCCs associated with cAMP/PKA and JNK signaling pathway. Cancer Med. 2019, 8, 3047–3058. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Wu, X.; Li, W.; Yan, Q.; Zhou, P.; Xia, Y.; Yao, W.; Zhu, F. HERV-W ENV Induces Innate Immune Activation and Neuronal Apoptosis via linc01930/cGAS Axis in Recent-Onset Schizophrenia. Int. J. Mol. Sci. 2023, 24, 3000. [Google Scholar] [CrossRef]
- Scott, E.C.; Devine, S.E. The Role of Somatic L1 Retrotransposition in Human Cancers. Viruses 2017, 9, 131. [Google Scholar] [CrossRef]
- Burn, A.; Roy, F.; Freeman, M.; Coffin, J.M. Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues. PLoS Biol. 2022, 20, e3001826. [Google Scholar] [CrossRef] [PubMed]
- She, J.; Du, M.; Xu, Z.; Jin, Y.; Li, Y.; Zhang, D.; Tao, C.; Chen, J.; Wang, J.; Yang, E. The landscape of hervRNAs transcribed from human endogenous retroviruses across human body sites. Genome Biol. 2022, 23, 231. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Etxebarria, K.; Sistiaga-Poveda, M.; Jugo, B.M. Endogenous retroviruses in domestic animals. Curr. Genom. 2014, 15, 256–265. [Google Scholar] [CrossRef]
- Bendall, M.L.; de Mulder, M.; Iniguez, L.P.; Lecanda-Sanchez, A.; Perez-Losada, M.; Ostrowski, M.A.; Jones, R.B.; Mulder, L.C.F.; Reyes-Teran, G.; Crandall, K.A.; et al. Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression. PLoS Comput. Biol. 2019, 15, e1006453. [Google Scholar] [CrossRef]
- Steiner, M.C.; Marston, J.L.; Iniguez, L.P.; Bendall, M.L.; Chiappinelli, K.B.; Nixon, D.F.; Crandall, K.A. Locus-Specific Characterization of Human Endogenous Retrovirus Expression in Prostate, Breast, and Colon Cancers. Cancer Res. 2021, 81, 3449–3460. [Google Scholar] [CrossRef]
- Shukla, S.; Zhang, X.; Niknafs, Y.S.; Xiao, L.; Mehra, R.; Cieslik, M.; Ross, A.; Schaeffer, E.; Malik, B.; Guo, S.; et al. Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer. Neoplasia 2016, 18, 489–499. [Google Scholar] [CrossRef] [PubMed]
- Bhardwaj, N.; Montesion, M.; Roy, F.; Coffin, J.M. Differential expression of HERV-K (HML-2) proviruses in cells and virions of the teratocarcinoma cell line Tera-1. Viruses 2015, 7, 939–968. [Google Scholar] [CrossRef]
- Houle, A.A.; Gibling, H.; Lamaze, F.C.; Edgington, H.A.; Soave, D.; Fave, M.J.; Agbessi, M.; Bruat, V.; Stein, L.D.; Awadalla, P. Aberrant PRDM9 expression impacts the pan-cancer genomic landscape. Genome Res. 2018, 28, 1611–1620. [Google Scholar] [CrossRef] [PubMed]
- Tomlins, S.A.; Laxman, B.; Dhanasekaran, S.M.; Helgeson, B.E.; Cao, X.; Morris, D.S.; Menon, A.; Jing, X.; Cao, Q.; Han, B.; et al. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 2007, 448, 595–599. [Google Scholar] [CrossRef]
- Attig, J.; Young, G.R.; Hosie, L.; Perkins, D.; Encheva-Yokoya, V.; Stoye, J.P.; Snijders, A.P.; Ternette, N.; Kassiotis, G. LTR retroelement expansion of the human cancer transcriptome and immunopeptidome revealed by de novo transcript assembly. Genome Res. 2019, 29, 1578–1590. [Google Scholar] [CrossRef]
- Chiappinelli, K.B.; Strissel, P.L.; Desrichard, A.; Li, H.; Henke, C.; Akman, B.; Hein, A.; Rote, N.S.; Cope, L.M.; Snyder, A.; et al. Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses. Cell 2016, 164, 1073. [Google Scholar] [CrossRef] [PubMed]
- Roulois, D.; Loo Yau, H.; Singhania, R.; Wang, Y.; Danesh, A.; Shen, S.Y.; Han, H.; Liang, G.; Jones, P.A.; Pugh, T.J.; et al. DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts. Cell 2015, 162, 961–973. [Google Scholar] [CrossRef]
- Mehdipour, P.; Marhon, S.A.; Ettayebi, I.; Chakravarthy, A.; Hosseini, A.; Wang, Y.; de Castro, F.A.; Loo Yau, H.; Ishak, C.; Abelson, S.; et al. Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency. Nature 2020, 588, 169–173. [Google Scholar] [CrossRef] [PubMed]
- de Cubas, A.A.; Dunker, W.; Zaninovich, A.; Hongo, R.A.; Bhatia, A.; Panda, A.; Beckermann, K.E.; Bhanot, G.; Ganesan, S.; Karijolich, J.; et al. DNA hypomethylation promotes transposable element expression and activation of immune signaling in renal cell cancer. JCI Insight 2020, 5, 137569. [Google Scholar] [CrossRef] [PubMed]
- Cortesi, A.; Gandolfi, F.; Arco, F.; Di Chiaro, P.; Valli, E.; Polletti, S.; Noberini, R.; Gualdrini, F.; Attanasio, S.; Citron, F.; et al. Activation of endogenous retroviruses and induction of viral mimicry by MEK1/2 inhibition in pancreatic cancer. Sci. Adv. 2024, 10, eadk5386. [Google Scholar] [CrossRef]
- Canadas, I.; Thummalapalli, R.; Kim, J.W.; Kitajima, S.; Jenkins, R.W.; Christensen, C.L.; Campisi, M.; Kuang, Y.; Zhang, Y.; Gjini, E.; et al. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat. Med. 2018, 24, 1143–1150. [Google Scholar] [CrossRef]
- Guo, Y.; Mao, X.; Xiong, L.; Xia, A.; You, J.; Lin, G.; Wu, C.; Huang, L.; Wang, Y.; Yang, S. Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain. Angew. Chem. Int. Ed. Engl. 2021, 60, 8760–8765. [Google Scholar] [CrossRef]
- Zanre, V.; Bellinato, F.; Cardile, A.; Passarini, C.; Monticelli, J.; Di Bella, S.; Menegazzi, M. Lamivudine, Doravirine, and Cabotegravir Downregulate the Expression of Human Endogenous Retroviruses (HERVs), Inhibit Cell Growth, and Reduce Invasive Capability in Melanoma Cell Lines. Int. J. Mol. Sci. 2024, 25, 1615. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Hu, L.; Wu, Z.; Yuan, K.; Hong, G.; Lian, Z.; Feng, J.; Li, N.; Li, D.; Wong, J.; et al. Loss of PHF8 induces a viral mimicry response by activating endogenous retrotransposons. Nat. Commun. 2023, 14, 4225. [Google Scholar] [CrossRef]
- Griffin, G.K.; Wu, J.; Iracheta-Vellve, A.; Patti, J.C.; Hsu, J.; Davis, T.; Dele-Oni, D.; Du, P.P.; Halawi, A.G.; Ishizuka, J.J.; et al. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity. Nature 2021, 595, 309–314. [Google Scholar] [CrossRef]
- Yang, B.; Fang, L.; Gao, Q.; Xu, C.; Xu, J.; Chen, Z.X.; Wang, Y.; Yang, P. Species-specific KRAB-ZFPs function as repressors of retroviruses by targeting PBS regions. Proc. Natl. Acad. Sci. USA 2022, 119, e2119415119. [Google Scholar] [CrossRef] [PubMed]
- Martins, F.; Rosspopoff, O.; Carlevaro-Fita, J.; Forey, R.; Offner, S.; Planet, E.; Pulver, C.; Pak, H.; Huber, F.; Michaux, J.; et al. A Cluster of Evolutionarily Recent KRAB Zinc Finger Proteins Protects Cancer Cells from Replicative Stress-Induced Inflammation. Cancer Res. 2024, 84, 808–826. [Google Scholar] [CrossRef] [PubMed]
- Hosseini, A.; Lindholm, H.T.; Chen, R.; Mehdipour, P.; Marhon, S.A.; Ishak, C.A.; Moore, P.C.; Classon, M.; Di Gioacchino, A.; Greenbaum, B.; et al. Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer. Cell Rep. 2024, 43, 113684. [Google Scholar] [CrossRef] [PubMed]
- Sun, M.A.; Wolf, G.; Wang, Y.; Senft, A.D.; Ralls, S.; Jin, J.; Dunn-Fletcher, C.E.; Muglia, L.J.; Macfarlan, T.S. Endogenous Retroviruses Drive Lineage-Specific Regulatory Evolution across Primate and Rodent Placentae. Mol. Biol. Evol. 2021, 38, 4992–5004. [Google Scholar] [CrossRef] [PubMed]
- Frost, J.M.; Amante, S.M.; Okae, H.; Jones, E.M.; Ashley, B.; Lewis, R.M.; Cleal, J.K.; Caley, M.P.; Arima, T.; Maffucci, T.; et al. Regulation of human trophoblast gene expression by endogenous retroviruses. Nat. Struct. Mol. Biol. 2023, 30, 527–538. [Google Scholar] [CrossRef] [PubMed]
- Landry, J.R.; Rouhi, A.; Medstrand, P.; Mager, D.L. The Opitz syndrome gene Mid1 is transcribed from a human endogenous retroviral promoter. Mol. Biol. Evol. 2002, 19, 1934–1942. [Google Scholar] [CrossRef] [PubMed]
- Adu-Gyamfi, E.A.; Cheeran, E.A.; Salamah, J.; Enabulele, D.B.; Tahir, A.; Lee, B.K. Long non-coding RNAs: A summary of their roles in placenta development and pathologydagger. Biol. Reprod. 2024, 110, 431–449. [Google Scholar] [CrossRef] [PubMed]
- Kong, X.; Li, R.; Chen, M.; Zheng, R.; Wang, J.; Sun, C.; Qu, Y. Endogenous retrovirus HERVH-derived lncRNA UCA1 controls human trophoblast development. Proc. Natl. Acad. Sci. USA 2024, 121, e2318176121. [Google Scholar] [CrossRef] [PubMed]
- Costanzo, V.; Bardelli, A.; Siena, S.; Abrignani, S. Exploring the links between cancer and placenta development. Open Biol. 2018, 8, 180081. [Google Scholar] [CrossRef]
- Smith, Z.D.; Shi, J.; Gu, H.; Donaghey, J.; Clement, K.; Cacchiarelli, D.; Gnirke, A.; Michor, F.; Meissner, A. Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer. Nature 2017, 549, 543–547. [Google Scholar] [CrossRef]
- Lynch-Sutherland, C.F.; Chatterjee, A.; Stockwell, P.A.; Eccles, M.R.; Macaulay, E.C. Reawakening the Developmental Origins of Cancer Through Transposable Elements. Front. Oncol. 2020, 10, 468. [Google Scholar] [CrossRef] [PubMed]
- Iurlaro, M.; von Meyenn, F.; Reik, W. DNA methylation homeostasis in human and mouse development. Curr. Opin. Genet. Dev. 2017, 43, 101–109. [Google Scholar] [CrossRef]
- Du, Z.; Zheng, H.; Huang, B.; Ma, R.; Wu, J.; Zhang, X.; He, J.; Xiang, Y.; Wang, Q.; Li, Y.; et al. Allelic reprogramming of 3D chromatin architecture during early mammalian development. Nature 2017, 547, 232–235. [Google Scholar] [CrossRef]
- Macfarlan, T.S.; Gifford, W.D.; Driscoll, S.; Lettieri, K.; Rowe, H.M.; Bonanomi, D.; Firth, A.; Singer, O.; Trono, D.; Pfaff, S.L. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 2012, 487, 57–63. [Google Scholar] [CrossRef]
- Taubenschmid-Stowers, J.; Rostovskaya, M.; Santos, F.; Ljung, S.; Argelaguet, R.; Krueger, F.; Nichols, J.; Reik, W. 8C-like cells capture the human zygotic genome activation program in vitro. Cell Stem Cell 2022, 29, 449–459 e446. [Google Scholar] [CrossRef] [PubMed]
- Asami, M.; Lam, B.Y.H.; Hoffmann, M.; Suzuki, T.; Lu, X.; Yoshida, N.; Ma, M.K.; Rainbow, K.; Guzvic, M.; VerMilyea, M.D.; et al. A program of successive gene expression in mouse one-cell embryos. Cell Rep. 2023, 42, 112023. [Google Scholar] [CrossRef]
- Asami, M.; Lam, B.Y.H.; Ma, M.K.; Rainbow, K.; Braun, S.; VerMilyea, M.D.; Yeo, G.S.H.; Perry, A.C.F. Human embryonic genome activation initiates at the one-cell stage. Cell Stem Cell 2022, 29, 209–216 e204. [Google Scholar] [CrossRef] [PubMed]
- Goke, J.; Lu, X.; Chan, Y.S.; Ng, H.H.; Ly, L.H.; Sachs, F.; Szczerbinska, I. Dynamic transcription of distinct classes of endogenous retroviral elements marks specific populations of early human embryonic cells. Cell Stem Cell 2015, 16, 135–141. [Google Scholar] [CrossRef]
- Grow, E.J.; Flynn, R.A.; Chavez, S.L.; Bayless, N.L.; Wossidlo, M.; Wesche, D.J.; Martin, L.; Ware, C.B.; Blish, C.A.; Chang, H.Y.; et al. Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells. Nature 2015, 522, 221–225. [Google Scholar] [CrossRef]
- Zhang, W.; Chen, F.; Chen, R.; Xie, D.; Yang, J.; Zhao, X.; Guo, R.; Zhang, Y.; Shen, Y.; Goke, J.; et al. Zscan4c activates endogenous retrovirus MERVL and cleavage embryo genes. Nucleic Acids Res. 2019, 47, 8485–8501. [Google Scholar] [CrossRef]
- Halstead, M.M.; Ma, X.; Zhou, C.; Schultz, R.M.; Ross, P.J. Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation. Nat. Commun. 2020, 11, 4654. [Google Scholar] [CrossRef] [PubMed]
- Nip, Y.; Bennett, S.R.; Smith, A.A.; Jones, T.I.; Jones, P.L.; Tapscott, S.J. Human DUX4 and porcine DUXC activate similar early embryonic programs in pig muscle cells: Implications for preclinical models of FSHD. Hum. Mol. Genet. 2023, 32, 1864–1874. [Google Scholar] [CrossRef] [PubMed]
- Wong, C.J.; Whiddon, J.L.; Langford, A.T.; Belleville, A.E.; Tapscott, S.J. Canine DUXC: Implications for DUX4 retrotransposition and preclinical models of FSHD. Hum. Mol. Genet. 2022, 31, 1694–1704. [Google Scholar] [CrossRef] [PubMed]
- Han, D.; Liu, G.; Oh, Y.; Oh, S.; Yang, S.; Mandjikian, L.; Rani, N.; Almeida, M.C.; Kosik, K.S.; Jang, J. ZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells. Nat. Commun. 2023, 14, 632. [Google Scholar] [CrossRef] [PubMed]
- Hendrickson, P.G.; Dorais, J.A.; Grow, E.J.; Whiddon, J.L.; Lim, J.W.; Wike, C.L.; Weaver, B.D.; Pflueger, C.; Emery, B.R.; Wilcox, A.L.; et al. Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Nat. Genet. 2017, 49, 925–934. [Google Scholar] [CrossRef] [PubMed]
- Ren, W.; Gao, L.; Mou, Y.; Deng, W.; Hua, J.; Yang, F. DUX: One Transcription Factor Controls 2-Cell-like Fate. Int. J. Mol. Sci. 2022, 23, 2067. [Google Scholar] [CrossRef] [PubMed]
- Smith, C.M.; Grow, E.J.; Shadle, S.C.; Cairns, B.R. Multiple repeat regions within mouse DUX recruit chromatin regulators to facilitate an embryonic gene expression program. bioRxiv 2023. [Google Scholar] [CrossRef]
- Whiddon, J.L.; Langford, A.T.; Wong, C.J.; Zhong, J.W.; Tapscott, S.J. Conservation and innovation in the DUX4-family gene network. Nat. Genet. 2017, 49, 935–940. [Google Scholar] [CrossRef]
- Maksakova, I.A.; Thompson, P.J.; Goyal, P.; Jones, S.J.; Singh, P.B.; Karimi, M.M.; Lorincz, M.C. Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells. Epigenetics Chromatin 2013, 6, 15. [Google Scholar] [CrossRef]
- Sakashita, A.; Kitano, T.; Ishizu, H.; Guo, Y.; Masuda, H.; Ariura, M.; Murano, K.; Siomi, H. Transcription of MERVL retrotransposons is required for preimplantation embryo development. Nat. Genet. 2023, 55, 484–495. [Google Scholar] [CrossRef]
- Xie, S.Q.; Leeke, B.J.; Whilding, C.; Wagner, R.T.; Garcia-Llagostera, F.; Low, Y.; Chammas, P.; Cheung, N.T.; Dormann, D.; McManus, M.T.; et al. Nucleolar-based Dux repression is essential for embryonic two-cell stage exit. Genes. Dev. 2022, 36, 331–347. [Google Scholar] [CrossRef] [PubMed]
- Vega-Sendino, M.; Luttmann, F.F.; Olbrich, T.; Chen, Y.; Kuenne, C.; Stein, P.; Tillo, D.; Carey, G.I.; Zhong, J.; Savy, V.; et al. The homeobox transcription factor DUXBL controls exit from totipotency. Nat. Genet. 2024, 56, 697–709. [Google Scholar] [CrossRef] [PubMed]
- Ye, Y.; Homer, H.A. A surge in cytoplasmic viscosity triggers nuclear remodeling required for Dux silencing and pre-implantation embryo development. Cell Rep. 2024, 43, 113917. [Google Scholar] [CrossRef] [PubMed]
- Ribet, D.; Louvet-Vallee, S.; Harper, F.; de Parseval, N.; Dewannieux, M.; Heidmann, O.; Pierron, G.; Maro, B.; Heidmann, T. Murine endogenous retrovirus MuERV-L is the progenitor of the “orphan” epsilon viruslike particles of the early mouse embryo. J. Virol. 2008, 82, 1622–1625. [Google Scholar] [CrossRef] [PubMed]
- de la Rosa, S.; Del Mar Rigual, M.; Vargiu, P.; Ortega, S.; Djouder, N. Endogenous retroviruses shape pluripotency specification in mouse embryos. Sci. Adv. 2024, 10, eadk9394. [Google Scholar] [CrossRef]
- Best, S.; Le Tissier, P.; Towers, G.; Stoye, J.P. Positional cloning of the mouse retrovirus restriction gene Fv1. Nature 1996, 382, 826–829. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Leng, L.; Liu, C.; Lu, C.; Yuan, Y.; Wu, L.; Gong, F.; Zhang, S.; Wei, X.; Wang, M.; et al. An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos. Nat. Commun. 2019, 10, 364. [Google Scholar] [CrossRef] [PubMed]
- Vuoristo, S.; Bhagat, S.; Hyden-Granskog, C.; Yoshihara, M.; Gawriyski, L.; Jouhilahti, E.M.; Ranga, V.; Tamirat, M.; Huhtala, M.; Kirjanov, I.; et al. DUX4 is a multifunctional factor priming human embryonic genome activation. iScience 2022, 25, 104137. [Google Scholar] [CrossRef] [PubMed]
- Hashimoto, K.; Jouhilahti, E.M.; Tohonen, V.; Carninci, P.; Kere, J.; Katayama, S. Embryonic LTR retrotransposons supply promoter modules to somatic tissues. Genome Res. 2021, 31, 1983–1993. [Google Scholar] [CrossRef]
- DiRusso, J.A.; Clark, A.T. Transposable elements in early human embryo development and embryo models. Curr. Opin. Genet. Dev. 2023, 81, 102086. [Google Scholar] [CrossRef]
- Mitsuhashi, S.; Nakagawa, S.; Sasaki-Honda, M.; Sakurai, H.; Frith, M.C.; Mitsuhashi, H. Nanopore direct RNA sequencing detects DUX4-activated repeats and isoforms in human muscle cells. Hum. Mol. Genet. 2021, 30, 552–563. [Google Scholar] [CrossRef] [PubMed]
- Chew, G.L.; Campbell, A.E.; De Neef, E.; Sutliff, N.A.; Shadle, S.C.; Tapscott, S.J.; Bradley, R.K. DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade. Dev. Cell 2019, 50, 658–671 e657. [Google Scholar] [CrossRef] [PubMed]
- Smith, A.A.; Nip, Y.; Bennett, S.R.; Hamm, D.C.; Lemmers, R.; van der Vliet, P.J.; Setty, M.; van der Maarel, S.M.; Tapscott, S.J. DUX4 expression in cancer induces a metastable early embryonic totipotent program. Cell Rep. 2023, 42, 113114. [Google Scholar] [CrossRef]
- Santoni, F.A.; Guerra, J.; Luban, J. HERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency. Retrovirology 2012, 9, 111. [Google Scholar] [CrossRef]
- Wang, J.; Xie, G.; Singh, M.; Ghanbarian, A.T.; Rasko, T.; Szvetnik, A.; Cai, H.; Besser, D.; Prigione, A.; Fuchs, N.V.; et al. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells. Nature 2014, 516, 405–409. [Google Scholar] [CrossRef] [PubMed]
- Ohnuki, M.; Tanabe, K.; Sutou, K.; Teramoto, I.; Sawamura, Y.; Narita, M.; Nakamura, M.; Tokunaga, Y.; Nakamura, M.; Watanabe, A.; et al. Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential. Proc. Natl. Acad. Sci. USA 2014, 111, 12426–12431. [Google Scholar] [CrossRef]
- Sexton, C.E.; Tillett, R.L.; Han, M.V. The essential but enigmatic regulatory role of HERVH in pluripotency. Trends Genet. 2022, 38, 12–21. [Google Scholar] [CrossRef]
- Lu, X.; Sachs, F.; Ramsay, L.; Jacques, P.E.; Goke, J.; Bourque, G.; Ng, H.H. The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nat. Struct. Mol. Biol. 2014, 21, 423–425. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Li, T.; Preissl, S.; Amaral, M.L.; Grinstein, J.D.; Farah, E.N.; Destici, E.; Qiu, Y.; Hu, R.; Lee, A.Y.; et al. Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. Nat. Genet. 2019, 51, 1380–1388. [Google Scholar] [CrossRef] [PubMed]
- Katzourakis, A.; Pereira, V.; Tristem, M. Effects of recombination rate on human endogenous retrovirus fixation and persistence. J. Virol. 2007, 81, 10712–10717. [Google Scholar] [CrossRef]
- Fuentes, D.R.; Swigut, T.; Wysocka, J. Systematic perturbation of retroviral LTRs reveals widespread long-range effects on human gene regulation. Elife 2018, 7, e35989. [Google Scholar] [CrossRef] [PubMed]
- Leidenroth, A.; Clapp, J.; Mitchell, L.M.; Coneyworth, D.; Dearden, F.L.; Iannuzzi, L.; Hewitt, J.E. Evolution of DUX gene macrosatellites in placental mammals. Chromosoma 2012, 121, 489–497. [Google Scholar] [CrossRef] [PubMed]
- Bosnakovski, D.; Toso, E.A.; Ener, E.T.; Gearhart, M.D.; Yin, L.; Luttmann, F.F.; Magli, A.; Shi, K.; Kim, J.; Aihara, H.; et al. Antagonism among DUX family members evolved from an ancestral toxic single homeodomain protein. iScience 2023, 26, 107823. [Google Scholar] [CrossRef] [PubMed]
- Jagannathan, S. The evolution of DUX4 gene regulation and its implication for facioscapulohumeral muscular dystrophy. Biochim. Biophys. Acta Mol. Basis Dis. 2022, 1868, 166367. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.K.; Bosnakovski, D.; Toso, E.A.; Dinh, T.; Banerjee, S.; Bohl, T.E.; Shi, K.; Orellana, K.; Kyba, M.; Aihara, H. Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA. Cell Rep. 2018, 25, 2955–2962 e2953. [Google Scholar] [CrossRef]
- Halo, J.V.; Pendleton, A.L.; Shen, F.; Doucet, A.J.; Derrien, T.; Hitte, C.; Kirby, L.E.; Myers, B.; Sliwerska, E.; Emery, S.; et al. Long-read assembly of a Great Dane genome highlights the contribution of GC-rich sequence and mobile elements to canine genomes. Proc. Natl. Acad. Sci. USA 2021, 118, e2016274118. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Jarosz, A.S.; Halo, J.V. Transcription of Endogenous Retroviruses: Broad and Precise Mechanisms of Control. Viruses 2024, 16, 1312. https://doi.org/10.3390/v16081312
Jarosz AS, Halo JV. Transcription of Endogenous Retroviruses: Broad and Precise Mechanisms of Control. Viruses. 2024; 16(8):1312. https://doi.org/10.3390/v16081312
Chicago/Turabian StyleJarosz, Abigail S., and Julia V. Halo. 2024. "Transcription of Endogenous Retroviruses: Broad and Precise Mechanisms of Control" Viruses 16, no. 8: 1312. https://doi.org/10.3390/v16081312