Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1990 Mar 11;18(5):1261–1270. doi: 10.1093/nar/18.5.1261

Functional heterogeneity of a large family of human LTR-like promoters and enhancers.

A Feuchter 1, D Mager 1
PMCID: PMC330443  PMID: 1690875

Abstract

The human genome contains a variety of elements similar in structure to retroviruses and retrotransposons. We have shown that the long terminal repeat (LTR) sequences of a large family of human retrovirus-like elements, RTVL-H, are heterogeneous in their ability to regulate the expression of linked genes. Although all of five LTRs tested could promote expression of the chloramphenicol acetyltransferase (CAT) gene, their relative promoter activities as well as range of activities varied widely. Several of the LTRs tested also exhibited bidirectional promoter activity either alone or when activated by an SV40 early enhancer. One LTR, H6, displayed strong promoter activity in human (NTera2D1, 293, Hep2), monkey (COS-1), and mouse (3T3) cells. In fact, the activity of this LTR was similar to that of the SV40 early promoter/enhancer in 293, COS-1, and 3T3 cells. RNA mapping studies have localized the transcription start site to the expected location in the H6 LTR. RTVL-H LTRs were also shown to contain sequences which could increase transcription from the human beta-globin promoter and be influenced by SV40 enhancer sequences. As the human genome contains several hundred related RTVL-H sequences and a similar number of solitary LTRs, these findings raise the possibility that RTVL-H LTRs could have diverse effects on the expression of adjacent cellular genes.

Full text

PDF
1261

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams S. E., Rathjen P. D., Stanway C. A., Fulton S. M., Malim M. H., Wilson W., Ogden J., King L., Kingsman S. M., Kingsman A. J. Complete nucleotide sequence of a mouse VL30 retro-element. Mol Cell Biol. 1988 Aug;8(8):2989–2998. doi: 10.1128/mcb.8.8.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews P. W., Damjanov I., Simon D., Banting G. S., Carlin C., Dracopoli N. C., Føgh J. Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro. Lab Invest. 1984 Feb;50(2):147–162. [PubMed] [Google Scholar]
  3. Banville D., Boie Y. Retroviral long terminal repeat is the promoter of the gene encoding the tumor-associated calcium-binding protein oncomodulin in the rat. J Mol Biol. 1989 Jun 5;207(3):481–490. doi: 10.1016/0022-2836(89)90458-0. [DOI] [PubMed] [Google Scholar]
  4. Blatt C., Aberdam D., Schwartz R., Sachs L. DNA rearrangement of a homeobox gene in myeloid leukaemic cells. EMBO J. 1988 Dec 20;7(13):4283–4290. doi: 10.1002/j.1460-2075.1988.tb03326.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen H. R., Barker W. C. Nucleotide sequences of the retroviral long terminal repeats and their adjacent regions. Nucleic Acids Res. 1984 Feb 24;12(4):1767–1778. doi: 10.1093/nar/12.4.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Christy R. J., Huang R. C. Functional analysis of the long terminal repeats of intracisternal A-particle genes: sequences within the U3 region determine both the efficiency and direction of promoter activity. Mol Cell Biol. 1988 Mar;8(3):1093–1102. doi: 10.1128/mcb.8.3.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen J. B., Unger T., Rechavi G., Canaani E., Givol D. Rearrangement of the oncogene c-mos in mouse myeloma NSI and hybridomas. Nature. 1983 Dec 22;306(5945):797–799. doi: 10.1038/306797a0. [DOI] [PubMed] [Google Scholar]
  8. Cohen M., Larsson E. Human endogenous retroviruses. Bioessays. 1988 Dec;9(6):191–196. doi: 10.1002/bies.950090603. [DOI] [PubMed] [Google Scholar]
  9. Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
  10. Finnegan D. J. Transposable elements in eukaryotes. Int Rev Cytol. 1985;93:281–326. doi: 10.1016/s0074-7696(08)61376-5. [DOI] [PubMed] [Google Scholar]
  11. Gattoni-Celli S., Hsiao W. L., Weinstein I. B. Rearranged c-mos locus in a MOPC 21 murine myeloma cell line and its persistence in hybridomas. Nature. 1983 Dec 22;306(5945):795–796. doi: 10.1038/306795a0. [DOI] [PubMed] [Google Scholar]
  12. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  14. Grosveld G. C., de Boer E., Shewmaker C. K., Flavell R. A. DNA sequences necessary for transcription of the rabbit beta-globin gene in vivo. Nature. 1982 Jan 14;295(5845):120–126. doi: 10.1038/295120a0. [DOI] [PubMed] [Google Scholar]
  15. Hawley R. G., Shulman M. J., Murialdo H., Gibson D. M., Hozumi N. Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7425–7429. doi: 10.1073/pnas.79.23.7425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Henthorn P., Zervos P., Raducha M., Harris H., Kadesch T. Expression of a human placental alkaline phosphatase gene in transfected cells: use as a reporter for studies of gene expression. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6342–6346. doi: 10.1073/pnas.85.17.6342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hilberg F., Stocking C., Ostertag W., Grez M. Functional analysis of a retroviral host-range mutant: altered long terminal repeat sequences allow expression in embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5232–5236. doi: 10.1073/pnas.84.15.5232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johansen T., Holm T., Bjørklid E. Members of the RTVL-H family of human endogenous retrovirus-like elements are expressed in placenta. Gene. 1989 Jul 15;79(2):259–267. doi: 10.1016/0378-1119(89)90208-4. [DOI] [PubMed] [Google Scholar]
  19. Kadesch T., Berg P. Effects of the position of the simian virus 40 enhancer on expression of multiple transcription units in a single plasmid. Mol Cell Biol. 1986 Jul;6(7):2593–2601. doi: 10.1128/mcb.6.7.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kadesch T., Zervos P., Ruezinsky D. Functional analysis of the murine IgH enhancer: evidence for negative control of cell-type specificity. Nucleic Acids Res. 1986 Oct 24;14(20):8209–8221. doi: 10.1093/nar/14.20.8209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kingsman A. J., Kingsman S. M. Ty: a retroelement moving forward. Cell. 1988 May 6;53(3):333–335. doi: 10.1016/0092-8674(88)90151-1. [DOI] [PubMed] [Google Scholar]
  22. Kongsuwan K., Allen J., Adams J. M. Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia. Nucleic Acids Res. 1989 Mar 11;17(5):1881–1892. doi: 10.1093/nar/17.5.1881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Larsson E., Kato N., Cohen M. Human endogenous proviruses. Curr Top Microbiol Immunol. 1989;148:115–132. doi: 10.1007/978-3-642-74700-7_4. [DOI] [PubMed] [Google Scholar]
  24. Lavappa K. S. Survey of ATCC stocks of human cell lines for HeLa contamination. In Vitro. 1978 May;14(5):469–475. doi: 10.1007/BF02616110. [DOI] [PubMed] [Google Scholar]
  25. Mager D. L., Freeman J. D. Human endogenous retroviruslike genome with type C pol sequences and gag sequences related to human T-cell lymphotropic viruses. J Virol. 1987 Dec;61(12):4060–4066. doi: 10.1128/jvi.61.12.4060-4066.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mager D. L., Goodchild N. L. Homologous recombination between the LTRs of a human retrovirus-like element causes a 5-kb deletion in two siblings. Am J Hum Genet. 1989 Dec;45(6):848–854. [PMC free article] [PubMed] [Google Scholar]
  27. Mager D. L., Henthorn P. S. Identification of a retrovirus-like repetitive element in human DNA. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7510–7514. doi: 10.1073/pnas.81.23.7510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mager D. L. Polyadenylation function and sequence variability of the long terminal repeats of the human endogenous retrovirus-like family RTVL-H. Virology. 1989 Dec;173(2):591–599. doi: 10.1016/0042-6822(89)90570-9. [DOI] [PubMed] [Google Scholar]
  29. Man Y. M., Delius H., Leader D. P. Molecular analysis of elements inserted into mouse gamma-actin processed pseudogenes. Nucleic Acids Res. 1987 Apr 24;15(8):3291–3304. doi: 10.1093/nar/15.8.3291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  31. O'Connell C. D., Cohen M. The long terminal repeat sequences of a novel human endogenous retrovirus. Science. 1984 Dec 7;226(4679):1204–1206. doi: 10.1126/science.6505687. [DOI] [PubMed] [Google Scholar]
  32. Ono M., Yasunaga T., Miyata T., Ushikubo H. Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome. J Virol. 1986 Nov;60(2):589–598. doi: 10.1128/jvi.60.2.589-598.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Paulson K. E., Deka N., Schmid C. W., Misra R., Schindler C. W., Rush M. G., Kadyk L., Leinwand L. A transposon-like element in human DNA. Nature. 1985 Jul 25;316(6026):359–361. doi: 10.1038/316359a0. [DOI] [PubMed] [Google Scholar]
  34. Paulson K. E., Matera A. G., Deka N., Schmid C. W. Transcription of a human transposon-like sequence is usually directed by other promoters. Nucleic Acids Res. 1987 Jul 10;15(13):5199–5215. doi: 10.1093/nar/15.13.5199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rochford R., Campbell B. A., Villarreal L. P. A pancreas specificity results from the combination of polyomavirus and Moloney murine leukemia virus enhancer. Proc Natl Acad Sci U S A. 1987 Jan;84(2):449–453. doi: 10.1073/pnas.84.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stavenhagen J. B., Robins D. M. An ancient provirus has imposed androgen regulation on the adjacent mouse sex-limited protein gene. Cell. 1988 Oct 21;55(2):247–254. doi: 10.1016/0092-8674(88)90047-5. [DOI] [PubMed] [Google Scholar]
  37. Steele P. E., Rabson A. B., Bryan T., Martin M. A. Distinctive termini characterize two families of human endogenous retroviral sequences. Science. 1984 Aug 31;225(4665):943–947. doi: 10.1126/science.6089336. [DOI] [PubMed] [Google Scholar]
  38. Tabor S., Richardson C. C. DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767–4771. doi: 10.1073/pnas.84.14.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Temin H. M. Structure, variation and synthesis of retrovirus long terminal repeat. Cell. 1981 Nov;27(1 Pt 2):1–3. doi: 10.1016/0092-8674(81)90353-6. [DOI] [PubMed] [Google Scholar]
  40. Varmus H. E. Form and function of retroviral proviruses. Science. 1982 May 21;216(4548):812–820. doi: 10.1126/science.6177038. [DOI] [PubMed] [Google Scholar]
  41. Ymer S., Tucker W. Q., Sanderson C. J., Hapel A. J., Campbell H. D., Young I. G. Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene. Nature. 1985 Sep 19;317(6034):255–258. doi: 10.1038/317255a0. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES