Abstract
Glucocorticoid hormones enhance the transcription of mouse mammary tumor virus DNA by mechanisms involving a direct interaction of the hormone receptor with four binding sites in a glucocorticoid regulatory element located between -72 and -192 base pairs upstream of the main transcription initiation site within the proviral long terminal repeat regions. Methylation at the N-7 position of any of three G residues within one of the binding sites prevents binding of the receptor. In addition, in the presence of the receptor, methylation by dimethyl sulfate is reduced at several G residues, indicating sites of contact between the receptor and DNA at these positions. The G residues in the hexanucleotide 5'-T-G-T-T-C-T-3' 3'-A-C-A-A-G-A-5' were protected by the receptor against MH2-specific gene. (iii) myc is followed by the 3'-terminal c region of about 400 nucleotides, which is colinear with that of Rous sarcoma virus except for a substitution near the 5' end of the long terminal repeat. It is concluded that MH2 contains two genes with oncogenic potential, the delta gag- mht gene, which is closely related to the delta gag-raf transforming gene of MSV 3611, and the myc gene, which is related to the transforming gene of MC29. Furthermore, it may be concluded that the cellular proto-onc genes, which on sequence transduction become viral onc genes, are a small group because among the 19 known onc sequences, 5 are shared by different taxonomic groups of viruses of which the mht /raf homology is the closest determined so far.
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PDF![3029](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff20/345214/0a3098309b4f/pnas00611-0092.png)
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Selected References
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- Chandler V. L., Maler B. A., Yamamoto K. R. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell. 1983 Jun;33(2):489–499. doi: 10.1016/0092-8674(83)90430-0. [DOI] [PubMed] [Google Scholar]
- Fasel N., Pearson K., Buetti E., Diggelmann H. The region of mouse mammary tumor virus DNA containing the long terminal repeat includes a long coding sequence and signals for hormonally regulated transcription. EMBO J. 1982;1(1):3–7. doi: 10.1002/j.1460-2075.1982.tb01115.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geisse S., Scheidereit C., Westphal H. M., Hynes N. E., Groner B., Beato M. Glucocorticoid receptors recognize DNA sequences in and around murine mammary tumour virus DNA. EMBO J. 1982;1(12):1613–1619. doi: 10.1002/j.1460-2075.1982.tb01363.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groner B., Ponta H., Beato M., Hynes N. E. The proviral DNA of mouse mammary tumor virus: its use in the study of the molecular details of steroid hormone action. Mol Cell Endocrinol. 1983 Oct;32(2-3):101–116. doi: 10.1016/0303-7207(83)90075-8. [DOI] [PubMed] [Google Scholar]
- Hynes N., van Ooyen A. J., Kennedy N., Herrlich P., Ponta H., Groner B. Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3637–3641. doi: 10.1073/pnas.80.12.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Ogata R. T., Gilbert W. An amino-terminal fragment of lac repressor binds specifically to lac operator. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5851–5854. doi: 10.1073/pnas.75.12.5851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross W., Landy A. Patterns of lambda Int recognition in the regions of strand exchange. Cell. 1983 May;33(1):261–272. doi: 10.1016/0092-8674(83)90355-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scheidereit C., Geisse S., Westphal H. M., Beato M. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus. Nature. 1983 Aug 25;304(5928):749–752. doi: 10.1038/304749a0. [DOI] [PubMed] [Google Scholar]
- Siebenlist U., Gilbert W. Contacts between Escherichia coli RNA polymerase and an early promoter of phage T7. Proc Natl Acad Sci U S A. 1980 Jan;77(1):122–126. doi: 10.1073/pnas.77.1.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiher H., König M., Gruss P. Multiple point mutations affecting the simian virus 40 enhancer. Science. 1983 Feb 11;219(4585):626–631. doi: 10.1126/science.6297005. [DOI] [PubMed] [Google Scholar]
- Wrange O., Carlstedt-Duke J., Gustafsson J. A. Purification of the glucocorticoid receptor from rat liver cytosol. J Biol Chem. 1979 Sep 25;254(18):9284–9290. [PubMed] [Google Scholar]