Skip to main content

Genomic impact, chromosomal distribution and transcriptional regulation of HERV elements

Molecules and Cells volume 33, pages 539–544 (2012)Cite this article

Abstract

Human endogenous retroviruses (HERVs) mediate structural variation and genomic instability based on their multiple copy number, inherent ability to mobilize via reverse transcriptase, and high sequence similarity. Moreover, they undergo multiple amplification and retrotransposition events, resulting in the widespread distribution of complete or partial retroviral sequences throughout the primate genome. As such, HERV elements have played important biological roles in genome evolution, and their long terminal repeat (LTR) elements contain numerous regulatory sequences, including effective promoters, enhancers, polyadenylation signals, and transcription factorbinding sites. Lastly, HERV elements are capable of influencing the expression of neighboring genes, a process that also contributed to primate evolution.

This is a preview of subscription content, access via your institution.

References

  • Akopov, S.B., Nikolaev, L.G., Khil, P.P., Lebedev, Y.B., and Sverdlov, E.D. (1998). Long terminal repeats of human endogenous retrovirus K family (HERV-K) specifically bind host cell nuclear proteins. FEBS Lett. 421, 229–223.

    PubMed  Article  CAS  Google Scholar 

  • Barbulescu, M., Turner, G., Seaman, M.I., Deinard, A.S., Kidd, K.K., and Lenz, J. (1999). Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans. Curr. Biol. 9, 861–868.

    PubMed  Article  CAS  Google Scholar 

  • Bourque, G., Leong, B., Vega, V.B., Chen, X., Lee, Y.L., Srinivasan, K.G., Chew, J.L., Ruan, Y., Wei, C.L., Ng, H.H., et al. (2008). Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res. 18, 1752–1762.

    PubMed  Article  CAS  Google Scholar 

  • Buzdin, A., Ustyugova, S., Khodosevich, K., Mamedov, I., Lebedev, Y., Hunsmann, G., and Sverdlov, E. (2003). Human-specific subfamilies of HERV-K (HML-2) long terminal repeats: three master genes were active simultaneously during branching of hominoid lineages. Genomics 81, 149–156.

    PubMed  Article  CAS  Google Scholar 

  • Buzdin, A., Vinogradova, T., Lebedev, Y., and Sverdlov, E. (2005). Genome-wide experimental identification and functional analysis of human specific retroelements. Cytogenet. Genome Res. 110, 468–474.

    PubMed  Article  CAS  Google Scholar 

  • Cohen, C.J., Lock, W.M., and Mager, D.L. (2009). Endogenous retroviral LTRs as promoters for human genes: a critical assessment. Gene 448, 105–114.

    PubMed  Article  CAS  Google Scholar 

  • Cohen, C.J., Rebollo, R., Babovic, S., Dai, E.L., Robinson, W.P., and Mager, D.L. (2011). Placenta-specific expression of the interleukin-2 (IL-2) receptor β subunit from an endogenous retroviral promoter. J. Biol. Chem. 286, 35543–35552.

    PubMed  Article  CAS  Google Scholar 

  • Costas, J. (2000). Characterization of the intragenomic spread of the human endogenous retrovirus family HERV-W. Mol. Biol. Evol. 19, 526–533.

    Article  Google Scholar 

  • Dangel, A.W., Baker, B.J., Mendoza, A.R., and Yu, C.Y. (1995). Complement component C4 gene intron 9 as a phylogenetic marker for primates: long terminal repeats of the endogenous retrovirus ERV-K(C4) are a molecular clock of evolution. Immunogenetics 42, 41–52.

    PubMed  Article  CAS  Google Scholar 

  • de Parseval, N., Casella, J., Gressin, L., and Heidmann, T. (2001). Characterization of the three HERV-H proviruses with an open envelope reading frame encompassing the immunosuppressive domain and evolutionary history in primates. Virology 279, 558–569.

    PubMed  Article  Google Scholar 

  • Domansky, A.N., Kopantzev, E.P., Snezhkov, E.V., Lebedev, Y.B., Leib-Mosch, C., and Sverdlov, E.D. (2000). Solitary HERV-K LTRs possess bi-directional promoter activity and contain a negative regulatory element in the U5 region. FEBS Lett. 472, 191–195.

    PubMed  Article  CAS  Google Scholar 

  • Dunn, C.A., Romanish, M.T., Gutierrez, L.E., van de Lagemaat, L.N., and Mager, D.L. (2006). Transcription of two human genes from a bidirectional endogenous retrovirus promoter. Gene 366, 335–342.

    PubMed  Article  CAS  Google Scholar 

  • Ego, T., Tanaka, T., and Shimotohno, K. (2005). Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR. Oncogene 24, 1914–1923.

    PubMed  Article  CAS  Google Scholar 

  • Gerlo, S., Davis, J.R., Mager, D.L., and Kooijman, R. (2006). Prolactin in man: a tale of two promoters. Bioessays 28, 1051–1055.

    PubMed  Article  CAS  Google Scholar 

  • Ha, H.S., Chung, W.K., Ahn, K., Bae, J.H., Park, S.J., Moon, J.W., Nam, K.H., Han, K., Cho, H., and Kim, H.S. (2011). Development of GEBRET: a web-based analysis tool for retroelements in primate genomes. Genes Genomics 33, 679–684.

    Article  CAS  Google Scholar 

  • Hughes, J.F., and Coffin, J.M. (2004). Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: implications for human and viral evolution. Proc. Natl. Acad. Sci. USA 101, 1668–1672.

    PubMed  Article  CAS  Google Scholar 

  • Huh, J.W., Ha, H.S., Kim, D.S., and Kim, H.S. (2008). Placentarestricted expression of LTR-derived NOS3. Placenta 29, 602–608.

    PubMed  Article  CAS  Google Scholar 

  • Huh, J.W., Kim, Y.H., Lee, S.R., Kim, H., Kim, D.S., Kim, H.S., Kang, H.S., and Chang, K.T. (2009). Gain of new exons and promoters by lineage-specific transposable elements-integration and conservation event on CHRM3 gene. Mol. Cells 28, 111–117.

    PubMed  Article  CAS  Google Scholar 

  • International Human Genome Sequencing Consortium (2001). Initial sequencing and analysis of the human genome. Nature 409, 860–921.

    Article  Google Scholar 

  • Kamat, A., Hinshelwood, M.M., Murry, B.A., and Mendelson, C.R. (2002). Mechanisms in tissue-specific regulation of estrogen biosynthesis in humans. Trends Endocrinol. Metab. 13, 122–128.

    PubMed  Article  CAS  Google Scholar 

  • Kamp, C., Hirschmann, P., Voss, H., Huellen, K., and Vogt, P.H. (2000). Two long homologous retroviral sequence blocks in proximal Yq11 cause AZFa microdeletions as a result of intrachromosomal recombination events. Hum. Mol. Genet. 9, 2563–2572.

    PubMed  Article  CAS  Google Scholar 

  • Kapitonov, V.V., and Jurka, J. (1999). The long terminal repeat of an endogenous retrovirus induces alternative splicing and encode an additional carboxy-terminal sequence in the human leptin receptor. J. Mol. Evol. 48, 248–251.

    PubMed  Article  CAS  Google Scholar 

  • Kim, H.S. (2001). Sequence and phylogeny of HERV-W pol fragments. AIDS Res. Hum. Retroviruses 17, 1665–1671.

    PubMed  Article  CAS  Google Scholar 

  • Kim, H.S., Wadekar, R.V., Takenaka, O., Winstanley, C., Mitsunaga, F., Kageyama, T., Hyun, B.H., and Crow, T.J. (1999). SINE. C2 (a Homo sapiens specific retroposon) is homologous to CDNA from postmortem brain in schizophrenia and to two loci in the Xq21.3/Yp block linked to handedness and psychosis. Am. J. Med. Genet. 88, 560–566.

    PubMed  Article  CAS  Google Scholar 

  • Kovalskaya, E., Buzdin, A., Gogvadze, E., Vinogradova, T., and Sverdlov, E. (2006). Functional human endogenous retroviral LTR transcription start sites are located between the R and U5 regions. Virology 346, 373–378.

    PubMed  Article  CAS  Google Scholar 

  • Kuzmin, D., Gogvadze, E., Kholodenko, R., Grzela, D.P., Mityaev, M., Vinogradova, T., Kopantzev, E., Malakhova, G., Suntsova, M., Sokov, D., et al. (2010). Novel strong tissue specific promoter for gene expression in human germ cells. BMC Biotechnol. 17, 58–68.

    Article  Google Scholar 

  • Landry, J.R., and Mager, D.L. (2003). Functional analysis of the endogenous retroviral promoter of the human endothelin B receptor gene. J. Virol. 77, 7459–7466.

    PubMed  Article  CAS  Google Scholar 

  • Landry, J.R., Rouhi, A., Medstrand, P., and Mager, D.L. (2002). The Opitz syndrome gene Mid1 is transcribed from a human endogenous retroviral promoter. Mol. Biol. Evol. 19, 1934–1942.

    PubMed  Article  CAS  Google Scholar 

  • Larsson, E., Kato, N., and Cohen, M. (1989). Human endogenous proviruses. Curr. Top. Microbiol. Immunol. 148, 115–132.

    PubMed  Article  CAS  Google Scholar 

  • Locke, D.P., Hillier, L.W., Warren, W.C., Worley, K.C., Nazareth, L.V., Muzny, D.M., Yang, S.P., Wang, Z., Chinwalla, A.T., Minx, P., et al. (2011). Comparative and demographic analysis of orangutan genomes. Nature 469, 529–533.

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Macfarlane, C., and Simmonds, P. (2004). Allelic variation of HERV-K(HML-2) endogenous retroviral elements in human populations. J. Mol. Evol. 59, 642–656.

    PubMed  Article  CAS  Google Scholar 

  • Mager, D.L., and Freeman, J.D. (1995). HERV-H endogenous retro-viruses: presence in the New World branch but amplification in the Old World primate lineage. Virology 213, 395–404.

    PubMed  Article  CAS  Google Scholar 

  • Mager, D.L., Hunter, D.G., Schertzer, M., and Freeman, J.D. (1999). Endogenous retroviruses provide the primary polyadenylation signal for two new human genes (HHLA2 and HHLA3). Genomics 59, 255–263.

    PubMed  Article  CAS  Google Scholar 

  • Medstrand, P., and Mager, D.L. (1998). Human-specific integrations of the HERV-K endogenous retrovirus family. J. Virol. 72, 9782–9787.

    PubMed  CAS  Google Scholar 

  • Medstrand, P., Landry, J.R., and Mager, D.L. (2001). Long terminal repeats are used as alternative promoters for the endothelin B receptor and apolipoprotein C-I genes in humans. J. Biol. Chem. 276, 1896–1903.

    PubMed  Article  CAS  Google Scholar 

  • Ono, M. (1986). Molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types A and B retrovirus genes. J. Virol. 58, 937–944.

    PubMed  CAS  Google Scholar 

  • Park, S.J., Huh, J.W., Kim, D.S., Ha, H.S., Jung, Y.D., Ahn, K., Oh, K.B., Park, E.W., Chang, K.T., and Kim, H.S. (2010). Analysis of the molecular and regulatory properties of active porcine endogenous retrovirus gamma-1 long terminal repeats in kidney tissues of the NIH-miniature pig. Mol. Cells 30, 319–325.

    PubMed  Article  CAS  Google Scholar 

  • Sauter, M., Schommer, S., Kremmer, E., Remberger, K., Dölken, G., Lemm, I., Buck, M., Best, B., Neumann-Haefelin, D., and Mueller-Lantzsch, N. (1995). Human endogenous retrovirus K10: expression of Gag protein and detection of antibodies in patients with seminomas. J. Virol. 69, 414–421.

    PubMed  CAS  Google Scholar 

  • Schon, U., Seifarth, W., Baust, C., Hohenadl, C., Erfle, V., and Leib-Mosch, C. (2001). Cell type-specific expression and promoter activity of human endogenous retroviral long terminal repeats. Virology 279, 280–291.

    PubMed  Article  CAS  Google Scholar 

  • Schulte, A.M., Lai, S., Kurtz, A., Czubayko, F., Riegel, A.T., and Wellstein, A. (1996). Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germline insertion of an endogenous retrovirus. Proc. Natl. Acad. Sci. USA 93, 14759–14764.

    PubMed  Article  CAS  Google Scholar 

  • Sin, H.S., Huh, J.W., Kim, D.S., Kang, D.W., Min, D.S., Kim, T.H., Ha, H.S., Kim, H.H., Lee, S.Y., and Kim, H.S. (2006). Transcriptional control of the HERV-H LTR element of the GSDML gene in human tissues and cancer cells. Arch. Virol. 151, 1985–1994.

    PubMed  Article  CAS  Google Scholar 

  • Sin, H.S., Huh, J.W., Kim, W.Y., Kim, D.S., Ahn, K., Ha, H.S., and Kim, H.S. (2007). Long terminal repeats provide alternative polyadenylation signals to NADSYN1 gene. Korean J. Genet. 29, 395–401.

    CAS  Google Scholar 

  • Sverdlov, E.D. (2000). Retroviruses and primate evolution. Bioessays 22, 161–171.

    PubMed  Article  CAS  Google Scholar 

  • Swindle, C.S., Kim, H.G., and Klug, C.A. (2004). Mutation of CpGs in the murine stem cell virus retroviral vector long terminal repeat represses silencing in embryonic stem cells. J. Biol. Chem. 279, 34–41.

    PubMed  Article  CAS  Google Scholar 

  • Varmus, H.E. (1982). Form and function of retroviral proviruses. Science 216, 812–820.

    PubMed  Article  CAS  Google Scholar 

  • Venables, P.J., Brookes, S.M., Griffiths, D., Weiss, R.A., and Boyd, M.T. (1995). Abundance of an endogenous retroviral envelope protein in placental trophoblasts suggests a biological function. Virology 211, 589–592.

    PubMed  Article  CAS  Google Scholar 

  • Voisset, C., Bouton, O., Bedin, F., Duret, L., Mandrand, B., Mallet, F., and Paranhos-Baccala, G. (2000). Chromosomal distribution and coding capacity of the human endogenous retrovirus HERV-W family. AIDS Res. Hum. Retroviruses 16, 731–740.

    PubMed  Article  CAS  Google Scholar 

  • Xin, D., Hu, L., and Kong, X. (2008). Alternative promoters influence alternative splicing at the genomic level. PLoS One 3, e2377

    PubMed  Article  Google Scholar 

  • Yi, J.M., Kim, H.M., and Kim, H.S. (2004). Expression of the human endogenous retrovirus HERV-W family in various human tissues and cancer cells. J. Gen. Virol. 85, 1203–1210.

    PubMed  Article  CAS  Google Scholar 

  • Yi, J.M., Kim, H.M., and Kim, H.S. (2006). Human endogenous retrovirus HERV-H family in human tissues and cancer cells: expression, identification, and phylogeny. Cancer Lett. 231, 228–239.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 609-735, Korea

    Heui-Soo Kim

Authors
  1. Heui-Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heui-Soo Kim.

About this article

Cite this article

Kim, HS. Genomic impact, chromosomal distribution and transcriptional regulation of HERV elements. Mol Cells 33, 539–544 (2012). https://doi.org/10.1007/s10059-012-0037-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10059-012-0037-y

Keywords

  • chromosomal distribution
  • copy number
  • HERV
  • LTR elements
  • promoter