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. 1996 Nov 2;135(4):1163–1177. doi: 10.1083/jcb.135.4.1163

Distinct regions control transcriptional activation of the alpha1(VI) collagen promoter in different tissues of transgenic mice

PMCID: PMC2133380  PMID: 8922394

Abstract

To identify regions involved in tissue specific regulation of transcription of the alpha1(VI) collagen chain, transgenic mice were generated carrying various portions of the gene's 5'-flanking sequence fused to the E. coli beta-galactosidase gene. Analysis of the transgene expression pattern by X-gal staining of embryos revealed that: (a) The proximal 0.6 kb of promoter sequence activated transcription in mesenchymal cells at sites of insertion of superficial muscular aponeurosis into the skin; tendons were also faintly positive. (b) The region between -4.0 and -5.4 kb from the transcription start site was required for activation of the transgene in nerves. It also drove expression in joints, in intervertebral disks, and in subepidermal and vibrissae mesenchyme. (c) The fragment comprised within -6.2 and -7.5 kb was necessary for high level transcription in skeletal muscle and meninges. Positive cells in muscle were mostly mononuclear and probably included connective tissue elements, although staining of myoblasts was not ruled out. This fragment also activated expression in joints, in intervertebral disks, and in subepidermal and vibrissae mesenchyme. (d) beta-Galactosidase staining in vibrissae induced by the sequences -4.0 to -5.4 and -6.2 to -7.5 was not coincident: with the latter sequence labeled nuclei were found mainly in the ventral and posterior quadrant, and, histologically, in the outer layers of mesenchyme surrounding and between the follicles, whereas with the former the remaining quadrants were positive and expressing cells were mostly in the inner layers of the dermal sheath. (e) Other tissues, notably lung, adrenal gland, digestive tract, which produce high amounts of collagen type VI, did not stain for beta-galactosidase. (f) Central nervous system and retina, in which the endogenous gene is inactive, expressed the lacZ transgene in most lines. The data suggest that transcription of alpha1(VI) in different tissues is regulated by distinct sequence elements in a modular arrangement, a mechanism which confers high flexibility in the temporal and spatial pattern of expression during development.

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Selected References

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  1. Adams J. C., Watt F. M. Regulation of development and differentiation by the extracellular matrix. Development. 1993 Apr;117(4):1183–1198. doi: 10.1242/dev.117.4.1183. [DOI] [PubMed] [Google Scholar]
  2. Bidanset D. J., Guidry C., Rosenberg L. C., Choi H. U., Timpl R., Hook M. Binding of the proteoglycan decorin to collagen type VI. J Biol Chem. 1992 Mar 15;267(8):5250–5256. [PubMed] [Google Scholar]
  3. Bonaldo P., Piccolo S., Marvulli D., Volpin D., Marigo V., Bressan G. M. Murine alpha 1(VI) collagen chain. Complete amino acid sequence and identification of the gene promoter region. Matrix. 1993 May;13(3):223–233. doi: 10.1016/s0934-8832(11)80006-5. [DOI] [PubMed] [Google Scholar]
  4. Bonaldo P., Russo V., Bucciotti F., Doliana R., Colombatti A. Structural and functional features of the alpha 3 chain indicate a bridging role for chicken collagen VI in connective tissues. Biochemistry. 1990 Feb 6;29(5):1245–1254. doi: 10.1021/bi00457a021. [DOI] [PubMed] [Google Scholar]
  5. Bonnerot C., Nicolas J. F. Application of LacZ gene fusions to postimplantation development. Methods Enzymol. 1993;225:451–469. doi: 10.1016/0076-6879(93)25031-v. [DOI] [PubMed] [Google Scholar]
  6. Bruns R. R., Press W., Engvall E., Timpl R., Gross J. Type VI collagen in extracellular, 100-nm periodic filaments and fibrils: identification by immunoelectron microscopy. J Cell Biol. 1986 Aug;103(2):393–404. doi: 10.1083/jcb.103.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Colombatti A., Bonaldo P., Doliana R. Type A modules: interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins. Matrix. 1993 Jul;13(4):297–306. doi: 10.1016/s0934-8832(11)80025-9. [DOI] [PubMed] [Google Scholar]
  8. Colombatti A., Mucignat M. T., Bonaldo P. Secretion and matrix assembly of recombinant type VI collagen. J Biol Chem. 1995 Jun 2;270(22):13105–13111. doi: 10.1074/jbc.270.22.13105. [DOI] [PubMed] [Google Scholar]
  9. Dani C., Doglio A., Amri E. Z., Bardon S., Fort P., Bertrand B., Grimaldi P., Ailhaud G. Cloning and regulation of a mRNA specifically expressed in the preadipose state. J Biol Chem. 1989 Jun 15;264(17):10119–10125. [PubMed] [Google Scholar]
  10. DeSimone D. W. Adhesion and matrix in vertebrate development. Curr Opin Cell Biol. 1994 Oct;6(5):747–751. doi: 10.1016/0955-0674(94)90103-1. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Ibrahimi A., Bertrand B., Bardon S., Amri E. Z., Grimaldi P., Ailhaud G., Dani C. Cloning of alpha 2 chain of type VI collagen and expression during mouse development. Biochem J. 1993 Jan 1;289(Pt 1):141–147. doi: 10.1042/bj2890141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Juliano R. L., Haskill S. Signal transduction from the extracellular matrix. J Cell Biol. 1993 Feb;120(3):577–585. doi: 10.1083/jcb.120.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Keene D. R., Engvall E., Glanville R. W. Ultrastructure of type VI collagen in human skin and cartilage suggests an anchoring function for this filamentous network. J Cell Biol. 1988 Nov;107(5):1995–2006. doi: 10.1083/jcb.107.5.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lin C. Q., Bissell M. J. Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 1993 Jun;7(9):737–743. doi: 10.1096/fasebj.7.9.8330681. [DOI] [PubMed] [Google Scholar]
  16. Liska D. J., Reed M. J., Sage E. H., Bornstein P. Cell-specific expression of alpha 1(I) collagen-hGH minigenes in transgenic mice. J Cell Biol. 1994 May;125(3):695–704. doi: 10.1083/jcb.125.3.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lovell-Badge R. H., Bygrave A., Bradley A., Robertson E., Tilly R., Cheah K. S. Tissue-specific expression of the human type II collagen gene in mice. Proc Natl Acad Sci U S A. 1987 May;84(9):2803–2807. doi: 10.1073/pnas.84.9.2803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marvulli D., Volpin D., Bressan G. M. Spatial and temporal changes of type VI collagen expression during mouse development. Dev Dyn. 1996 Aug;206(4):447–454. doi: 10.1002/(SICI)1097-0177(199608)206:4<447::AID-AJA10>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  19. Mitz V., Peyronie M. The superficial musculo-aponeurotic system (SMAS) in the parotid and cheek area. Plast Reconstr Surg. 1976 Jul;58(1):80–88. doi: 10.1097/00006534-197607000-00013. [DOI] [PubMed] [Google Scholar]
  20. Niederreither K., D'Souza R. N., de Crombrugghe B. Minimal DNA sequences that control the cell lineage-specific expression of the pro alpha 2(I) collagen promoter in transgenic mice. J Cell Biol. 1992 Dec;119(5):1361–1370. doi: 10.1083/jcb.119.5.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pavlin D., Lichtler A. C., Bedalov A., Kream B. E., Harrison J. R., Thomas H. F., Gronowicz G. A., Clark S. H., Woody C. O., Rowe D. W. Differential utilization of regulatory domains within the alpha 1(I) collagen promoter in osseous and fibroblastic cells. J Cell Biol. 1992 Jan;116(1):227–236. doi: 10.1083/jcb.116.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Peltonen J., Jaakkola S., Hsiao L. L., Timpl R., Chu M. L., Uitto J. Type VI collagen. In situ hybridizations and immunohistochemistry reveal abundant mRNA and protein levels in human neurofibroma, schwannoma and normal peripheral nerve tissues. Lab Invest. 1990 Apr;62(4):487–492. [PubMed] [Google Scholar]
  23. Pfaff M., Aumailley M., Specks U., Knolle J., Zerwes H. G., Timpl R. Integrin and Arg-Gly-Asp dependence of cell adhesion to the native and unfolded triple helix of collagen type VI. Exp Cell Res. 1993 May;206(1):167–176. doi: 10.1006/excr.1993.1134. [DOI] [PubMed] [Google Scholar]
  24. Piccolo S., Bonaldo P., Vitale P., Volpin D., Bressan G. M. Transcriptional activation of the alpha 1(VI) collagen gene during myoblast differentiation is mediated by multiple GA boxes. J Biol Chem. 1995 Aug 18;270(33):19583–19590. doi: 10.1074/jbc.270.33.19583. [DOI] [PubMed] [Google Scholar]
  25. Quarto R., Dozin B., Bonaldo P., Cancedda R., Colombatti A. Type VI collagen expression is upregulated in the early events of chondrocyte differentiation. Development. 1993 Jan;117(1):245–251. doi: 10.1242/dev.117.1.245. [DOI] [PubMed] [Google Scholar]
  26. Rossert J., Eberspaecher H., de Crombrugghe B. Separate cis-acting DNA elements of the mouse pro-alpha 1(I) collagen promoter direct expression of reporter genes to different type I collagen-producing cells in transgenic mice. J Cell Biol. 1995 Jun;129(5):1421–1432. doi: 10.1083/jcb.129.5.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sham M. H., Vesque C., Nonchev S., Marshall H., Frain M., Gupta R. D., Whiting J., Wilkinson D., Charnay P., Krumlauf R. The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation. Cell. 1993 Jan 29;72(2):183–196. doi: 10.1016/0092-8674(93)90659-e. [DOI] [PubMed] [Google Scholar]
  28. Sokolov B. P., Ala-Kokko L., Dhulipala R., Arita M., Khillan J. S., Prockop D. J. Tissue-specific expression of the gene for type I procollagen (COL1A1) in transgenic mice. Only 476 base pairs of the promoter are required if collagen genes are used as reporters. J Biol Chem. 1995 Apr 21;270(16):9622–9629. doi: 10.1074/jbc.270.16.9622. [DOI] [PubMed] [Google Scholar]
  29. Specks U., Mayer U., Nischt R., Spissinger T., Mann K., Timpl R., Engel J., Chu M. L. Structure of recombinant N-terminal globule of type VI collagen alpha 3 chain and its binding to heparin and hyaluronan. EMBO J. 1992 Dec;11(12):4281–4290. doi: 10.1002/j.1460-2075.1992.tb05527.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vitadello M., Denis-Donini S. Expression of neurofilament proteins in granule cells of the cerebellum. Brain Res. 1990 Feb 12;509(1):47–54. doi: 10.1016/0006-8993(90)90307-w. [DOI] [PubMed] [Google Scholar]

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