Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 May;87(10):3778–3782. doi: 10.1073/pnas.87.10.3778

NICER elements: a family of nerve growth factor-inducible cAMP-extinguishable retrovirus-like elements.

K O Cho 1, B Minsk 1, J A Wagner 1
PMCID: PMC53986  PMID: 2160077

Abstract

We have shown previously that the transcription of the gene designated d5 is induced by nerve growth factor (NGF) in rat adrenal pheochromocytoma PC-12 cells and that this NGF induction is repressed by cAMP. In this paper we demonstrate that d5 is a member of a gene family that contains several hundred members, which is closely related to retroviruses and retrotransposons, as demonstrated by the following observations: (i) the original d5 cDNA hybridized to numerous restriction fragments in genomic DNA; (ii) d5 cDNA hybridized to genomic clones with various intensities, and genomic clones can be isolated with a frequency suggesting that this family includes several hundred members; and (iii) there were minor sequence variations in four independently isolated cDNA clones that were homologous to d5 cDNA. Primer extension studies show that initiation of the 5.7-kilobase d5 mRNA(s) occurs at a unique site relative to a synthetic primer. The 5' end of the cDNA sequence was homologous to Rasheed rat sarcoma virus; and a genomic clone contained several elements that are typical of a long terminal repeat (LTR), including a CCAAT box, a TATA box, a primer binding site, a poly(A) addition signal, and a poly(A) addition site. Furthermore, there is a LTR at the 3' end of at least one of the genes in this family, and there appeared to be a four-base duplication at the probable site of integration into host DNA. Since several members of this family retain responses to NGF and cAMP, we conclude that the regulatory elements present in the LTR have been conserved in many members of this family. We have named this family of genes the NICER elements because they are a family of NGF-inducible cAMP-extinguishable retrovirus-like elements.

Full text

PDF
3778

Images in this article

3780Image
on p.3780
3782Image
on p.3782

Selected References

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

  1. Ayer-LeLievre C., Olson L., Ebendal T., Hallbök F., Persson H. Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2628–2632. doi: 10.1073/pnas.85.8.2628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burt D. W., Reith A. D., Brammar W. J. A retroviral provirus closely associated with the Ren-2 gene of DBA/2 mice. Nucleic Acids Res. 1984 Nov 26;12(22):8579–8593. doi: 10.1093/nar/12.22.8579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Changelian P. S., Feng P., King T. C., Milbrandt J. Structure of the NGFI-A gene and detection of upstream sequences responsible for its transcriptional induction by nerve growth factor. Proc Natl Acad Sci U S A. 1989 Jan;86(1):377–381. doi: 10.1073/pnas.86.1.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cho K. O., Skarnes W. C., Minsk B., Palmieri S., Jackson-Grusby L., Wagner J. A. Nerve growth factor regulates gene expression by several distinct mechanisms. Mol Cell Biol. 1989 Jan;9(1):135–143. doi: 10.1128/mcb.9.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Finnegan D. J. Eukaryotic transposable elements and genome evolution. Trends Genet. 1989 Apr;5(4):103–107. doi: 10.1016/0168-9525(89)90039-5. [DOI] [PubMed] [Google Scholar]
  7. Foster D. N., Schmidt L. J., Hodgson C. P., Moses H. L., Getz M. J. Polyadenylylated RNA complementary to a mouse retrovirus-like multigene family is rapidly and specifically induced by epidermal growth factor stimulation of quiescent cells. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7317–7321. doi: 10.1073/pnas.79.23.7317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gilman M. Z., Wilson R. N., Weinberg R. A. Multiple protein-binding sites in the 5'-flanking region regulate c-fos expression. Mol Cell Biol. 1986 Dec;6(12):4305–4316. doi: 10.1128/mcb.6.12.4305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Greenberg M. E., Siegfried Z., Ziff E. B. Mutation of the c-fos gene dyad symmetry element inhibits serum inducibility of transcription in vivo and the nuclear regulatory factor binding in vitro. Mol Cell Biol. 1987 Mar;7(3):1217–1225. doi: 10.1128/mcb.7.3.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  11. Jones R. H., Moreno S., Nurse P., Jones N. C. Expression of the SV40 promoter in fission yeast: identification and characterization of an AP-1-like factor. Cell. 1988 May 20;53(4):659–667. doi: 10.1016/0092-8674(88)90581-8. [DOI] [PubMed] [Google Scholar]
  12. Miksicek R., Heber A., Schmid W., Danesch U., Posseckert G., Beato M., Schütz G. Glucocorticoid responsiveness of the transcriptional enhancer of Moloney murine sarcoma virus. Cell. 1986 Jul 18;46(2):283–290. doi: 10.1016/0092-8674(86)90745-2. [DOI] [PubMed] [Google Scholar]
  13. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  14. Rasheed S., Norman G. L., Heidecker G. Nucleotide sequence of the Rasheed rat sarcoma virus oncogene: new mutations. Science. 1983 Jul 8;221(4606):155–157. doi: 10.1126/science.6344220. [DOI] [PubMed] [Google Scholar]
  15. Rodland K. D., Brown A. M., Magun B. E. Individual mouse VL30 elements transferred to rat cells by viral pseudotypes retain their responsiveness to activators of protein kinase C. Mol Cell Biol. 1987 Jun;7(6):2296–2298. doi: 10.1128/mcb.7.6.2296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rodland K. D., Muldoon L. L., Dinh T. H., Magun B. E. Independent transcriptional regulation of a single VL30 element by epidermal growth factor and activators of protein kinase C. Mol Cell Biol. 1988 May;8(5):2247–2250. doi: 10.1128/mcb.8.5.2247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rubin G. M., Kidwell M. G., Bingham P. M. The molecular basis of P-M hybrid dysgenesis: the nature of induced mutations. Cell. 1982 Jul;29(3):987–994. doi: 10.1016/0092-8674(82)90462-7. [DOI] [PubMed] [Google Scholar]
  18. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sheng M., Dougan S. T., McFadden G., Greenberg M. E. Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences. Mol Cell Biol. 1988 Jul;8(7):2787–2796. doi: 10.1128/mcb.8.7.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Starcich B., Ratner L., Josephs S. F., Okamoto T., Gallo R. C., Wong-Staal F. Characterization of long terminal repeat sequences of HTLV-III. Science. 1985 Feb 1;227(4686):538–540. doi: 10.1126/science.2981438. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Tamkun J. W., Schwarzbauer J. E., Hynes R. O. A single rat fibronectin gene generates three different mRNAs by alternative splicing of a complex exon. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5140–5144. doi: 10.1073/pnas.81.16.5140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Treisman R. Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell. 1985 Oct;42(3):889–902. doi: 10.1016/0092-8674(85)90285-5. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES