Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1991 May;11(5):2826–2831. doi: 10.1128/mcb.11.5.2826

c-fos gene transcription in murine macrophages is modulated by a calcium-dependent block to elongation in intron 1.

M A Collart 1, N Tourkine 1, D Belin 1, P Vassalli 1, P Jeanteur 1, J M Blanchard 1
PMCID: PMC360065  PMID: 1901949

Abstract

Cultured mouse thioglycolate-elicited peritoneal macrophages exhibit a strong block to transcriptional elongation beyond the end of the c-fos gene first exon. This block is absent in freshly isolated peritoneal cells, appears slowly during culture, and does not require adherence of the cells. The extent of this block is largely responsible for the levels of c-fos mRNA in cultured macrophages, even after modulation by agents such as the tumor promoter phorbol myristate acetate and increased intracellular cyclic AMP, which also increase the activity of the c-fos promoter. When macrophages are cultured in the absence of mobilizable calcium, the block can no longer be relieved by any inducing agent. Conversely, upon calcium influxes, there is little alteration in the level of transcriptional initiation, but transcription proceeds efficiently through the entire c-fos locus. These results suggest the presence of an intragenic calcium-responsive element in the c-fos gene and illustrate its key role in the control of c-fos gene transcription.

Full text

PDF
2826

Images in this article

2827Image
on p.2827
2827Image
on p.2827
2828Image
on p.2828
2828Image
on p.2828

Selected References

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

  1. Bender T. P., Thompson C. B., Kuehl W. M. Differential expression of c-myb mRNA in murine B lymphomas by a block to transcription elongation. Science. 1987 Sep 18;237(4821):1473–1476. doi: 10.1126/science.3498214. [DOI] [PubMed] [Google Scholar]
  2. Bentley D. L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature. 1986 Jun 12;321(6071):702–706. doi: 10.1038/321702a0. [DOI] [PubMed] [Google Scholar]
  3. Bentley D. L., Groudine M. Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas. Mol Cell Biol. 1986 Oct;6(10):3481–3489. doi: 10.1128/mcb.6.10.3481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berkowitz L. A., Riabowol K. T., Gilman M. Z. Multiple sequence elements of a single functional class are required for cyclic AMP responsiveness of the mouse c-fos promoter. Mol Cell Biol. 1989 Oct;9(10):4272–4281. doi: 10.1128/mcb.9.10.4272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blanchard J. M., Piechaczyk M., Fort P., Bonnieu A., Mechti N., Rech J., Cuny M., Lebleu B., Jeanteur P. The regulatory strategies of c-myc and c-fos proto-oncogenes share some common mechanisms. Biochimie. 1988 Jul;70(7):877–884. doi: 10.1016/0300-9084(88)90228-3. [DOI] [PubMed] [Google Scholar]
  6. Bonnieu A., Rech J., Jeanteur P., Fort P. Requirements for c-fos mRNA down regulation in growth stimulated murine cells. Oncogene. 1989 Jul;4(7):881–888. [PubMed] [Google Scholar]
  7. Bravo R., Burckhardt J., Curran T., Müller R. Stimulation and inhibition of growth by EGF in different A431 cell clones is accompanied by the rapid induction of c-fos and c-myc proto-oncogenes. EMBO J. 1985 May;4(5):1193–1197. doi: 10.1002/j.1460-2075.1985.tb03759.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bravo R., Neuberg M., Burckhardt J., Almendral J., Wallich R., Müller R. Involvement of common and cell type-specific pathways in c-fos gene control: stable induction of cAMP in macrophages. Cell. 1987 Jan 30;48(2):251–260. doi: 10.1016/0092-8674(87)90428-4. [DOI] [PubMed] [Google Scholar]
  9. Cobbold P. H., Rink T. J. Fluorescence and bioluminescence measurement of cytoplasmic free calcium. Biochem J. 1987 Dec 1;248(2):313–328. doi: 10.1042/bj2480313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collart M. A., Belin D., Briottet C., Thorens B., Vassalli J. D., Vassalli P. Receptor-mediated phagocytosis by macrophages induces a calcium-dependent transient increase in c-fos transcription. Oncogene. 1989 Feb;4(2):237–241. [PubMed] [Google Scholar]
  11. Collart M. A., Belin D., Vassalli J. D., Vassalli P. Modulations of functional activity in differentiated macrophages are accompanied by early and transient increase or decrease in c-fos gene transcription. J Immunol. 1987 Aug 1;139(3):949–955. [PubMed] [Google Scholar]
  12. Eick D., Bornkamm G. W. Transcriptional arrest within the first exon is a fast control mechanism in c-myc gene expression. Nucleic Acids Res. 1986 Nov 11;14(21):8331–8346. doi: 10.1093/nar/14.21.8331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fisch T. M., Prywes R., Roeder R. G. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore. Mol Cell Biol. 1987 Oct;7(10):3490–3502. doi: 10.1128/mcb.7.10.3490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fisch T. M., Prywes R., Simon M. C., Roeder R. G. Multiple sequence elements in the c-fos promoter mediate induction by cAMP. Genes Dev. 1989 Feb;3(2):198–211. doi: 10.1101/gad.3.2.198. [DOI] [PubMed] [Google Scholar]
  15. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fort P., Rech J., Vie A., Piechaczyk M., Bonnieu A., Jeanteur P., Blanchard J. M. Regulation of c-fos gene expression in hamster fibroblasts: initiation and elongation of transcription and mRNA degradation. Nucleic Acids Res. 1987 Jul 24;15(14):5657–5667. doi: 10.1093/nar/15.14.5657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gilman M. Z., Berkowitz L. A., Feramisco J. R., Franza B. R., Jr, Graham R. M., Riabowol K. T., Ryan W. A., Jr Intracellular mediators of c-fos induction. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):761–767. doi: 10.1101/sqb.1988.053.01.086. [DOI] [PubMed] [Google Scholar]
  18. Gilman M. Z. The c-fos serum response element responds to protein kinase C-dependent and -independent signals but not to cyclic AMP. Genes Dev. 1988 Apr;2(4):394–402. doi: 10.1101/gad.2.4.394. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Greenberg M. E., Ziff E. B., Greene L. A. Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science. 1986 Oct 3;234(4772):80–83. doi: 10.1126/science.3749894. [DOI] [PubMed] [Google Scholar]
  21. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  22. Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
  23. Introna M., Hamilton T. A., Kaufman R. E., Adams D. O., Bast R. C., Jr Treatment of murine peritoneal macrophages with bacterial lipopolysaccharide alters expression of c-fos and c-myc oncogenes. J Immunol. 1986 Oct 15;137(8):2711–2715. [PubMed] [Google Scholar]
  24. Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
  25. Lamb N. J., Fernandez A., Tourkine N., Jeanteur P., Blanchard J. M. Demonstration in living cells of an intragenic negative regulatory element within the rodent c-fos gene. Cell. 1990 May 4;61(3):485–496. doi: 10.1016/0092-8674(90)90530-r. [DOI] [PubMed] [Google Scholar]
  26. Lin H. S., Stewart C. C. Peritoneal exudate cells. I. Growth requirement of cells capable of forming colonies in soft agar. J Cell Physiol. 1974 Jun;83(3):369–378. doi: 10.1002/jcp.1040830307. [DOI] [PubMed] [Google Scholar]
  27. Lindsten T., June C. H., Thompson C. B. Multiple mechanisms regulate c-myc gene expression during normal T cell activation. EMBO J. 1988 Sep;7(9):2787–2794. doi: 10.1002/j.1460-2075.1988.tb03133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mechti N., Piechaczyk M., Blanchard J. M., Jeanteur P., Lebleu B. Sequence requirements for premature transcription arrest within the first intron of the mouse c-fos gene. Mol Cell Biol. 1991 May;11(5):2832–2841. doi: 10.1128/mcb.11.5.2832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mechti N., Piechaczyk M., Blanchard J. M., Marty L., Bonnieu A., Jeanteur P., Lebleu B. Transcriptional and post-transcriptional regulation of c-myc expression during the differentiation of murine erythroleukemia Friend cells. Nucleic Acids Res. 1986 Dec 22;14(24):9653–9666. doi: 10.1093/nar/14.24.9653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Montesano R., Mossaz A., Vassalli P., Orci L. Specialization of the macrophage plasma membrane at sites of interaction with opsonized erythrocytes. J Cell Biol. 1983 May;96(5):1227–1233. doi: 10.1083/jcb.96.5.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Morgan J. I., Curran T. Role of ion flux in the control of c-fos expression. Nature. 1986 Aug 7;322(6079):552–555. doi: 10.1038/322552a0. [DOI] [PubMed] [Google Scholar]
  32. Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
  33. Nepveu A., Marcu K. B. Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO J. 1986 Nov;5(11):2859–2865. doi: 10.1002/j.1460-2075.1986.tb04580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Prywes R., Fisch T. M., Roeder R. G. Transcriptional regulation of c-fos. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):739–748. doi: 10.1101/sqb.1988.053.01.084. [DOI] [PubMed] [Google Scholar]
  35. Radzioch D., Bottazzi B., Varesio L. Augmentation of c-fos mRNA expression by activators of protein kinase C in fresh, terminally differentiated resting macrophages. Mol Cell Biol. 1987 Feb;7(2):595–599. doi: 10.1128/mcb.7.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sariban E., Luebbers R., Kufe D. Transcriptional and posttranscriptional control of c-fos gene expression in human monocytes. Mol Cell Biol. 1988 Jan;8(1):340–346. doi: 10.1128/mcb.8.1.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sassone-Corsi P., Visvader J., Ferland L., Mellon P. L., Verma I. M. Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element. Genes Dev. 1988 Dec;2(12A):1529–1538. doi: 10.1101/gad.2.12a.1529. [DOI] [PubMed] [Google Scholar]
  38. Schneider-Schaulies J., Schimpl A., Wecker E. Kinetics of cellular oncogene expression in mouse lymphocytes. II. Regulation of c-fos and c-myc gene expression. Eur J Immunol. 1987 May;17(5):713–718. doi: 10.1002/eji.1830170521. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Sheng M., McFadden G., Greenberg M. E. Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB. Neuron. 1990 Apr;4(4):571–582. doi: 10.1016/0896-6273(90)90115-v. [DOI] [PubMed] [Google Scholar]
  41. Shyu A. B., Greenberg M. E., Belasco J. G. The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev. 1989 Jan;3(1):60–72. doi: 10.1101/gad.3.1.60. [DOI] [PubMed] [Google Scholar]
  42. Sobczak J., Mechti N., Tournier M. F., Blanchard J. M., Duguet M. c-myc and c-fos gene regulation during mouse liver regeneration. Oncogene. 1989 Dec;4(12):1503–1508. [PubMed] [Google Scholar]
  43. Spencer C. A., Groudine M. Transcription elongation and eukaryotic gene regulation. Oncogene. 1990 Jun;5(6):777–785. [PubMed] [Google Scholar]
  44. Treisman R. The SRE: a growth factor responsive transcriptional regulator. Semin Cancer Biol. 1990 Feb;1(1):47–58. [PubMed] [Google Scholar]
  45. 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]
  46. Verma I. M., Sassone-Corsi P. Proto-oncogene fos: complex but versatile regulation. Cell. 1987 Nov 20;51(4):513–514. doi: 10.1016/0092-8674(87)90115-2. [DOI] [PubMed] [Google Scholar]
  47. Watson R. J. Expression of the c-myb and c-myc genes is regulated independently in differentiating mouse erythroleukemia cells by common processes of premature transcription arrest and increased mRNA turnover. Mol Cell Biol. 1988 Sep;8(9):3938–3942. doi: 10.1128/mcb.8.9.3938. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES