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. 1990 May;1(6):487–498. doi: 10.1091/mbc.1.6.487

A highly conserved intronic sequence is involved in transcriptional regulation of the alpha 1(I) collagen gene.

D J Liska 1, J L Slack 1, P Bornstein 1
PMCID: PMC361549  PMID: 2127540

Abstract

The first intron of the human alpha 1(I) collagen gene contains a positive, orientation-dependent cis-acting sequence located between bases +292 and +670. Transient transfection experiments indicate that this sequence is functional in both primary chicken tendon fibroblasts and in a human fibroblast-like cell line derived from SV40-transformed marrow stromal cells. DNase I footprint, methylation interference, and mobility shift analyses provide evidence for a sequence-specific binding activity and show that the region of binding corresponds to a 29-base-pair sequence that is also present in the rat alpha 1(I) collagen intron. This conserved sequence contains an AP1 consensus motif. Sequence-specific binding activity is present in nuclear extracts from HeLa and fibroblast cell lines but not in extracts from two lymphoid cell lines. Mutation of the AP1 consensus sequence indicates that this motif is required for function of the cis-acting element. These data indicate that transcriptional modulation of the alpha 1(I) collagen gene involves an interaction between an intronic AP1-containing sequence and its cognate transcription factors.

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Selected References

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

  1. Andrews D. F., 3rd, Nemunaitis J., Tompkins C., Singer J. W. Effect of 5-azacytidine on gene expression in marrow stromal cells. Mol Cell Biol. 1989 Jun;9(6):2748–2751. doi: 10.1128/mcb.9.6.2748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  3. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  4. Bornstein P., McKay J., Liska D. J., Apone S., Devarayalu S. Interactions between the promoter and first intron are involved in transcriptional control of alpha 1(I) collagen gene expression. Mol Cell Biol. 1988 Nov;8(11):4851–4857. doi: 10.1128/mcb.8.11.4851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bornstein P., McKay J., Morishima J. K., Devarayalu S., Gelinas R. E. Regulatory elements in the first intron contribute to transcriptional control of the human alpha 1(I) collagen gene. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8869–8873. doi: 10.1073/pnas.84.24.8869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bornstein P., McKay J. The first intron of the alpha 1(I) collagen gene contains several transcriptional regulatory elements. J Biol Chem. 1988 Feb 5;263(4):1603–1606. [PubMed] [Google Scholar]
  7. Bornstein P., Sage H. Regulation of collagen gene expression. Prog Nucleic Acid Res Mol Biol. 1989;37:67–106. doi: 10.1016/s0079-6603(08)60695-9. [DOI] [PubMed] [Google Scholar]
  8. Burbelo P. D., Martin G. R., Yamada Y. Alpha 1(IV) and alpha 2(IV) collagen genes are regulated by a bidirectional promoter and a shared enhancer. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9679–9682. doi: 10.1073/pnas.85.24.9679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chiu R., Angel P., Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell. 1989 Dec 22;59(6):979–986. doi: 10.1016/0092-8674(89)90754-x. [DOI] [PubMed] [Google Scholar]
  10. Choy H. A., McLaughlin M., Feigelson P. Nuclear factors from expressing tissues interact in vitro with a rat alpha-2u globulin gene intron. J Biol Chem. 1989 Jan 25;264(3):1754–1759. [PubMed] [Google Scholar]
  11. Delclos K. B., Blumberg P. M. Decrease in collagen production in normal and Rous sarcoma virus-transformed chick embryo fibroblasts induced by phorbol myristate acetate. Cancer Res. 1979 May;39(5):1667–1672. [PubMed] [Google Scholar]
  12. Dion L. D., Bear J., Bateman J., De Luca L. M., Colburn N. H. Inhibition by tumor-promoting phorbol esters of procollagen synthesis in promotable JB6 mouse epidermal cells. J Natl Cancer Inst. 1982 Nov;69(5):1147–1154. [PubMed] [Google Scholar]
  13. Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
  14. Galson D. L., Housman D. E. Detection of two tissue-specific DNA-binding proteins with affinity for sites in the mouse beta-globin intervening sequence 2. Mol Cell Biol. 1988 Jan;8(1):381–392. doi: 10.1128/mcb.8.1.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  16. Hallauer P. L., Hastings K. E., Peterson A. C. Fast skeletal muscle-specific expression of a quail troponin I gene in transgenic mice. Mol Cell Biol. 1988 Dec;8(12):5072–5079. doi: 10.1128/mcb.8.12.5072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hayashi S., Goto K., Okada T. S., Kondoh H. Lens-specific enhancer in the third intron regulates expression of the chicken delta 1-crystallin gene. Genes Dev. 1987 Oct;1(8):818–828. doi: 10.1101/gad.1.8.818. [DOI] [PubMed] [Google Scholar]
  18. Hirai S. I., Ryseck R. P., Mechta F., Bravo R., Yaniv M. Characterization of junD: a new member of the jun proto-oncogene family. EMBO J. 1989 May;8(5):1433–1439. doi: 10.1002/j.1460-2075.1989.tb03525.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Horton W., Miyashita T., Kohno K., Hassell J. R., Yamada Y. Identification of a phenotype-specific enhancer in the first intron of the rat collagen II gene. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8864–8868. doi: 10.1073/pnas.84.24.8864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kerr L. D., Holt J. T., Matrisian L. M. Growth factors regulate transin gene expression by c-fos-dependent and c-fos-independent pathways. Science. 1988 Dec 9;242(4884):1424–1427. doi: 10.1126/science.2462278. [DOI] [PubMed] [Google Scholar]
  21. Killen P. D., Burbelo P. D., Martin G. R., Yamada Y. Characterization of the promoter for the alpha 1 (IV) collagen gene. DNA sequences within the first intron enhance transcription. J Biol Chem. 1988 Sep 5;263(25):12310–12314. [PubMed] [Google Scholar]
  22. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  23. Li L., Hu J. S., Olson E. N. Different members of the jun proto-oncogene family exhibit distinct patterns of expression in response to type beta transforming growth factor. J Biol Chem. 1990 Jan 25;265(3):1556–1562. [PubMed] [Google Scholar]
  24. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  25. Mercola M., Wang X. F., Olsen J., Calame K. Transcriptional enhancer elements in the mouse immunoglobulin heavy chain locus. Science. 1983 Aug 12;221(4611):663–665. doi: 10.1126/science.6306772. [DOI] [PubMed] [Google Scholar]
  26. Müller M. M., Gerster T., Schaffner W. Enhancer sequences and the regulation of gene transcription. Eur J Biochem. 1988 Oct 1;176(3):485–495. doi: 10.1111/j.1432-1033.1988.tb14306.x. [DOI] [PubMed] [Google Scholar]
  27. Ng S. Y., Gunning P., Liu S. H., Leavitt J., Kedes L. Regulation of the human beta-actin promoter by upstream and intron domains. Nucleic Acids Res. 1989 Jan 25;17(2):601–615. doi: 10.1093/nar/17.2.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Penttinen R. P., Kobayashi S., Bornstein P. Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1105–1108. doi: 10.1073/pnas.85.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pertovaara L., Sistonen L., Bos T. J., Vogt P. K., Keski-Oja J., Alitalo K. Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation. Mol Cell Biol. 1989 Mar;9(3):1255–1262. doi: 10.1128/mcb.9.3.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Raghow R., Thompson J. P. Molecular mechanisms of collagen gene expression. Mol Cell Biochem. 1989 Mar 16;86(1):5–18. doi: 10.1007/BF00231686. [DOI] [PubMed] [Google Scholar]
  31. Rippe R. A., Lorenzen S. I., Brenner D. A., Breindl M. Regulatory elements in the 5'-flanking region and the first intron contribute to transcriptional control of the mouse alpha 1 type I collagen gene. Mol Cell Biol. 1989 May;9(5):2224–2227. doi: 10.1128/mcb.9.5.2224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Risse G., Jooss K., Neuberg M., Brüller H. J., Müller R. Asymmetrical recognition of the palindromic AP1 binding site (TRE) by Fos protein complexes. EMBO J. 1989 Dec 1;8(12):3825–3832. doi: 10.1002/j.1460-2075.1989.tb08560.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rossi P., Karsenty G., Roberts A. B., Roche N. S., Sporn M. B., de Crombrugghe B. A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-beta. Cell. 1988 Feb 12;52(3):405–414. doi: 10.1016/s0092-8674(88)80033-3. [DOI] [PubMed] [Google Scholar]
  34. Rossi P., de Crombrugghe B. Identification of a cell-specific transcriptional enhancer in the first intron of the mouse alpha 2 (type I) collagen gene. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5590–5594. doi: 10.1073/pnas.84.16.5590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rossouw C. M., Vergeer W. P., du Plooy S. J., Bernard M. P., Ramirez F., de Wet W. J. DNA sequences in the first intron of the human pro-alpha 1(I) collagen gene enhance transcription. J Biol Chem. 1987 Nov 5;262(31):15151–15157. [PubMed] [Google Scholar]
  36. Ryder K., Lau L. F., Nathans D. A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1487–1491. doi: 10.1073/pnas.85.5.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Saito H., Hayday A. C., Wiman K., Hayward W. S., Tonegawa S. Activation of the c-myc gene by translocation: a model for translational control. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7476–7480. doi: 10.1073/pnas.80.24.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sanders M. M., McKnight G. S. Positive and negative regulatory elements control the steroid-responsive ovalbumin promoter. Biochemistry. 1988 Aug 23;27(17):6550–6557. doi: 10.1021/bi00417a053. [DOI] [PubMed] [Google Scholar]
  39. Sassone-Corsi P., Sisson J. C., Verma I. M. Transcriptional autoregulation of the proto-oncogene fos. Nature. 1988 Jul 28;334(6180):314–319. doi: 10.1038/334314a0. [DOI] [PubMed] [Google Scholar]
  40. Schütte J., Viallet J., Nau M., Segal S., Fedorko J., Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell. 1989 Dec 22;59(6):987–997. doi: 10.1016/0092-8674(89)90755-1. [DOI] [PubMed] [Google Scholar]
  41. Shapiro D. J., Sharp P. A., Wahli W. W., Keller M. J. A high-efficiency HeLa cell nuclear transcription extract. DNA. 1988 Jan-Feb;7(1):47–55. doi: 10.1089/dna.1988.7.47. [DOI] [PubMed] [Google Scholar]
  42. Singer J. W., Charbord P., Keating A., Nemunaitis J., Raugi G., Wight T. N., Lopez J. A., Roth G. J., Dow L. W., Fialkow P. J. Simian virus 40-transformed adherent cells from human long-term marrow cultures: cloned cell lines produce cells with stromal and hematopoietic characteristics. Blood. 1987 Aug;70(2):464–474. [PubMed] [Google Scholar]
  43. Sobel M. E., Dion L. D., Vuust J., Colburn N. H. Tumor-promoting phorbol esters inhibit procollagen synthesis at a pretranslational level in JB-6 mouse epidermal cells. Mol Cell Biol. 1983 Aug;3(8):1527–1532. doi: 10.1128/mcb.3.8.1527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sternberg E. A., Spizz G., Perry W. M., Vizard D., Weil T., Olson E. N. Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene. Mol Cell Biol. 1988 Jul;8(7):2896–2909. doi: 10.1128/mcb.8.7.2896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Takimoto M., Quinn J. P., Farina A. R., Staudt L. M., Levens D. fos/jun and octamer-binding protein interact with a common site in a negative element of the human c-myc gene. J Biol Chem. 1989 May 25;264(15):8992–8999. [PubMed] [Google Scholar]
  46. Weiss A., Wiskocil R. L., Stobo J. D. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level. J Immunol. 1984 Jul;133(1):123–128. [PubMed] [Google Scholar]
  47. Yutzey K. E., Kline R. L., Konieczny S. F. An internal regulatory element controls troponin I gene expression. Mol Cell Biol. 1989 Apr;9(4):1397–1405. doi: 10.1128/mcb.9.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]

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