Skip to main content
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
. 1984 Dec;81(23):7392–7396. doi: 10.1073/pnas.81.23.7392

Duplicated heavy metal control sequences of the mouse metallothionein-I gene.

A D Carter, B K Felber, M J Walling, M F Jubier, C J Schmidt, D H Hamer
PMCID: PMC392152  PMID: 6095291

Abstract

We present evidence that two distinct regions of the DNA upstream from the mouse metallothionein-I gene contain metal-responsive regulatory sites. This result was obtained by analyzing a systematic series of deletion, insertion, duplication, and clustered point mutations introduced into cultured cells on a simian virus 40 plasmid vector. The two upstream regions contain a duplicated evolutionarily conserved DNA sequence. While either upstream region is sufficient to confer heavy metal responsiveness, both are required to give maximal levels of induced transcription.

Full text

PDF
7392

Images in this article

Selected References

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

  1. Brinster R. L., Chen H. Y., Warren R., Sarthy A., Palmiter R. D. Regulation of metallothionein--thymidine kinase fusion plasmids injected into mouse eggs. Nature. 1982 Mar 4;296(5852):39–42. doi: 10.1038/296039a0. [DOI] [PubMed] [Google Scholar]
  2. Durnam D. M., Palmiter R. D. Transcriptional regulation of the mouse metallothionein-I gene by heavy metals. J Biol Chem. 1981 Jun 10;256(11):5712–5716. [PubMed] [Google Scholar]
  3. Glanville N., Durnam D. M., Palmiter R. D. Structure of mouse metallothionein-I gene and its mRNA. Nature. 1981 Jul 16;292(5820):267–269. doi: 10.1038/292267a0. [DOI] [PubMed] [Google Scholar]
  4. Gorman C., Padmanabhan R., Howard B. H. High efficiency DNA-mediated transformation of primate cells. Science. 1983 Aug 5;221(4610):551–553. doi: 10.1126/science.6306768. [DOI] [PubMed] [Google Scholar]
  5. Hamer D. H., Walling M. Regulation in vivo of a cloned mammalian gene: cadmium induces the transcription of a mouse metallothionein gene in SV40 vectors. J Mol Appl Genet. 1982;1(4):273–288. [PubMed] [Google Scholar]
  6. Karin M., Andersen R. D., Slater E., Smith K., Herschman H. R. Metallothionein mRNA induction in HeLa cells in response to zinc or dexamethasone is a primary induction response. Nature. 1980 Jul 17;286(5770):295–297. doi: 10.1038/286295a0. [DOI] [PubMed] [Google Scholar]
  7. Karin M., Cathala G., Nguyen-Huu M. C. Expression and regulation of a human metallothionein gene carried on an autonomously replicating shuttle vector. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4040–4044. doi: 10.1073/pnas.80.13.4040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Karin M., Haslinger A., Holtgreve H., Cathala G., Slater E., Baxter J. D. Activation of a heterologous promoter in response to dexamethasone and cadmium by metallothionein gene 5'-flanking DNA. Cell. 1984 Feb;36(2):371–379. doi: 10.1016/0092-8674(84)90230-7. [DOI] [PubMed] [Google Scholar]
  9. Karin M., Haslinger A., Holtgreve H., Richards R. I., Krauter P., Westphal H. M., Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. doi: 10.1038/308513a0. [DOI] [PubMed] [Google Scholar]
  10. Karin M., Richards R. I. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene. Nature. 1982 Oct 28;299(5886):797–802. doi: 10.1038/299797a0. [DOI] [PubMed] [Google Scholar]
  11. Lusky M., Botchan M. Inhibition of SV40 replication in simian cells by specific pBR322 DNA sequences. Nature. 1981 Sep 3;293(5827):79–81. doi: 10.1038/293079a0. [DOI] [PubMed] [Google Scholar]
  12. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mayo K. E., Warren R., Palmiter R. D. The mouse metallothionein-I gene is transcriptionally regulated by cadmium following transfection into human or mouse cells. Cell. 1982 May;29(1):99–108. doi: 10.1016/0092-8674(82)90094-0. [DOI] [PubMed] [Google Scholar]
  14. McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
  15. Palmiter R. D., Chen H. Y., Brinster R. L. Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Cell. 1982 Jun;29(2):701–710. doi: 10.1016/0092-8674(82)90186-6. [DOI] [PubMed] [Google Scholar]
  16. Pavlakis G. N., Hamer D. H. Regulation of a metallothionein-growth hormone hybrid gene in bovine papilloma virus. Proc Natl Acad Sci U S A. 1983 Jan;80(2):397–401. doi: 10.1073/pnas.80.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schümperli D., Howard B. H., Rosenberg M. Efficient expression of Escherichia coli galactokinase gene in mammalian cells. Proc Natl Acad Sci U S A. 1982 Jan;79(2):257–261. doi: 10.1073/pnas.79.2.257. [DOI] [PMC free article] [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