Abstract
We have identified two blocks of regulatory sequences located in the 5'-flanking region and the first intron of the mouse alpha 1 type I collagen (COL1A1) gene. Both blocks were found to contain positive as well as negative regulatory elements. Sequences located within 222 base pairs upstream of the transcription start site showed a strong stimulatory effect on the COL1A1 promoter and were sufficient for tissue-specific regulation of the COL1A1 gene. The combined upstream and intron regulatory sequences showed a marked inhibition of COL1A1 promoter activity in fibroblasts. This finding suggests that additional, more remote regulatory sequences may be required for establishing the high level of activity of the endogenous COL1A1 gene in fibroblastoid cells.
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Selected References
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- Adams S. L., Alwine J. C., de Crombrugghe B., Pastan I. Use of recombinant plasmids to characterize collagen RNAs in normal and transformed chick embryo fibroblasts. J Biol Chem. 1979 Jun 25;254(12):4935–4938. [PubMed] [Google Scholar]
- 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]
- 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]
- Breindl M., Harbers K., Jaenisch R. Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure. Cell. 1984 Aug;38(1):9–16. doi: 10.1016/0092-8674(84)90521-x. [DOI] [PubMed] [Google Scholar]
- Choe I., Aycock R. S., Raghow R., Myers J. C., Seyer J. M., Kang A. H. A hepatic fibrogenic factor stimulates the synthesis of types I, III, and V procollagens in cultured cells. J Biol Chem. 1987 Apr 15;262(11):5408–5413. [PubMed] [Google Scholar]
- 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]
- Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
- Hall C. V., Jacob P. E., Ringold G. M., Lee F. Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells. J Mol Appl Genet. 1983;2(1):101–109. [PubMed] [Google Scholar]
- Harbers K., Kuehn M., Delius H., Jaenisch R. Insertion of retrovirus into the first intron of alpha 1(I) collagen gene to embryonic lethal mutation in mice. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1504–1508. doi: 10.1073/pnas.81.5.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hatamochi A., Paterson B., de Crombrugghe B. Differential binding of a CCAAT DNA binding factor to the promoters of the mouse alpha 2(I) and alpha 1(III) collagen genes. J Biol Chem. 1986 Aug 25;261(24):11310–11314. [PubMed] [Google Scholar]
- 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]
- Howard B. H., Adams S. L., Sobel M. E., Pastan I., de Crombrugghe B. Decreased levels of collagen mRNA in rous sarcoma virus-transformed chick embryo fibroblasts. J Biol Chem. 1978 Aug 25;253(16):5869–5874. [PubMed] [Google Scholar]
- Ignotz R. A., Endo T., Massagué J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J Biol Chem. 1987 May 15;262(14):6443–6446. [PubMed] [Google Scholar]
- Khillan J. S., Schmidt A., Overbeek P. A., de Crombrugghe B., Westphal H. Developmental and tissue-specific expression directed by the alpha 2 type I collagen promoter in transgenic mice. Proc Natl Acad Sci U S A. 1986 Feb;83(3):725–729. doi: 10.1073/pnas.83.3.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laimins L. A., Gruss P., Pozzatti R., Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. doi: 10.1128/jvi.49.1.183-189.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maity S. N., Golumbek P. T., Karsenty G., de Crombrugghe B. Selective activation of transcription by a novel CCAAT binding factor. Science. 1988 Jul 29;241(4865):582–585. doi: 10.1126/science.3399893. [DOI] [PubMed] [Google Scholar]
- Oikarinen J., Hatamochi A., de Crombrugghe B. Separate binding sites for nuclear factor 1 and a CCAAT DNA binding factor in the mouse alpha 2(I) collagen promoter. J Biol Chem. 1987 Aug 15;262(23):11064–11070. [PubMed] [Google Scholar]
- Pierce R. A., Glaug M. R., Greco R. S., Mackenzie J. W., Boyd C. D., Deak S. B. Increased procollagen mRNA levels in carbon tetrachloride-induced liver fibrosis in rats. J Biol Chem. 1987 Feb 5;262(4):1652–1658. [PubMed] [Google Scholar]
- Raghow R., Kang A. H., Pidikiti D. Phenotypic plasticity of extracellular matrix gene expression in cultured hamster lung fibroblasts. Regulation of type I procollagen and fibronectin synthesis. J Biol Chem. 1987 Jun 15;262(17):8409–8415. [PubMed] [Google Scholar]
- Rosenbloom J., Feldman G., Freundlich B., Jimenez S. A. Transcriptional control of human diploid fibroblast collagen synthesis by gamma-interferon. Biochem Biophys Res Commun. 1984 Aug 30;123(1):365–372. doi: 10.1016/0006-291x(84)90422-4. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Schmidt A., Rossi P., de Crombrugghe B. Transcriptional control of the mouse alpha 2(I) collagen gene: functional deletion analysis of the promoter and evidence for cell-specific expression. Mol Cell Biol. 1986 Feb;6(2):347–354. doi: 10.1128/mcb.6.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Solis-Herruzo J. A., Brenner D. A., Chojkier M. Tumor necrosis factor alpha inhibits collagen gene transcription and collagen synthesis in cultured human fibroblasts. J Biol Chem. 1988 Apr 25;263(12):5841–5845. [PubMed] [Google Scholar]
- Walsh M. J., LeLeiko N. S., Sterling K. M., Jr Regulation of types I, III, and IV procollagen mRNA synthesis in glucocorticoid-mediated intestinal development. J Biol Chem. 1987 Aug 5;262(22):10814–10818. [PubMed] [Google Scholar]