Abstract
Transfection experiments using Xenopus vitellogenin A2 gene constructs allowed us to identify an activator which increases the activity of the thymidine kinase promoter. The activator is located between -121 and -87 of the A2 vitellogenin gene and is separated by a stretch of curved DNA from the estrogen-responsive DNA element at -331. The activator functions in a cell-specific manner, as it is active in human breast cancer cells (MCF-7) as well as hepatoma cells but not in fibroblasts or HeLa cells. The activator is composed of at least three elements: elements 1 and 2 which form a partial palindrome, function independently, but act synergistically when combined. Element 3 is not active on its own, but supports elements 1 and 2. A TATA box region derived from the Xenopus albumin gene is sufficient for the function of the activator. In vitro transcription experiments using rat liver nuclear extracts demonstrate that the activator interacts with transcription factors. These factors are distinct from those recognizing HP1, a regulatory element common to several genes specifically expressed in hepatocytes.
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Selected References
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- Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
- Coon H. G., Weiss M. C. A quantitative comparison of formation of spontaneous and virus-produced viable hybrids. Proc Natl Acad Sci U S A. 1969 Mar;62(3):852–859. doi: 10.1073/pnas.62.3.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Simone V., Ciliberto G., Hardon E., Paonessa G., Palla F., Lundberg L., Cortese R. Cis- and trans-acting elements responsible for the cell-specific expression of the human alpha 1-antitrypsin gene. EMBO J. 1987 Sep;6(9):2759–2766. doi: 10.1002/j.1460-2075.1987.tb02570.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diekmann S. Sequence specificity of curved DNA. FEBS Lett. 1986 Jan 20;195(1-2):53–56. doi: 10.1016/0014-5793(86)80128-4. [DOI] [PubMed] [Google Scholar]
- Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Hsieh C. H., Griffith J. D. The terminus of SV40 DNA replication and transcription contains a sharp sequence-directed curve. Cell. 1988 Feb 26;52(4):535–544. doi: 10.1016/0092-8674(88)90466-7. [DOI] [PubMed] [Google Scholar]
- Huber S., Ryffel G. U., Weber R. Thyroid hormone induces competence for oestrogen-dependent vitellogenin synthesis in developing Xenopus laevis liver. Nature. 1979 Mar 1;278(5699):65–67. doi: 10.1038/278065a0. [DOI] [PubMed] [Google Scholar]
- Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
- Klein-Hitpass L., Kaling M., Ryffel G. U. Synergism of closely adjacent estrogen-responsive elements increases their regulatory potential. J Mol Biol. 1988 Jun 5;201(3):537–544. doi: 10.1016/0022-2836(88)90635-3. [DOI] [PubMed] [Google Scholar]
- Klein-Hitpass L., Ryffel G. U., Heitlinger E., Cato A. C. A 13 bp palindrome is a functional estrogen responsive element and interacts specifically with estrogen receptor. Nucleic Acids Res. 1988 Jan 25;16(2):647–663. doi: 10.1093/nar/16.2.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein-Hitpass L., Schorpp M., Wagner U., Ryffel G. U. An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell. 1986 Sep 26;46(7):1053–1061. doi: 10.1016/0092-8674(86)90705-1. [DOI] [PubMed] [Google Scholar]
- Koo H. S., Wu H. M., Crothers D. M. DNA bending at adenine . thymine tracts. Nature. 1986 Apr 10;320(6062):501–506. doi: 10.1038/320501a0. [DOI] [PubMed] [Google Scholar]
- Kugler W., Wagner U., Ryffel G. U. Tissue-specificity of liver gene expression: a common liver-specific promoter element. Nucleic Acids Res. 1988 Apr 25;16(8):3165–3174. doi: 10.1093/nar/16.8.3165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
- Marini J. C., Levene S. D., Crothers D. M., Englund P. T. Bent helical structure in kinetoplast DNA. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7664–7668. doi: 10.1073/pnas.79.24.7664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martinez E., Givel F., Wahli W. The estrogen-responsive element as an inducible enhancer: DNA sequence requirements and conversion to a glucocorticoid-responsive element. EMBO J. 1987 Dec 1;6(12):3719–3727. doi: 10.1002/j.1460-2075.1987.tb02706.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mohun T., Garrett N., Treisman R. Xenopus cytoskeletal actin and human c-fos gene promoters share a conserved protein-binding site. EMBO J. 1987 Mar;6(3):667–673. doi: 10.1002/j.1460-2075.1987.tb04806.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Satchwell S. C., Drew H. R., Travers A. A. Sequence periodicities in chicken nucleosome core DNA. J Mol Biol. 1986 Oct 20;191(4):659–675. doi: 10.1016/0022-2836(86)90452-3. [DOI] [PubMed] [Google Scholar]
- Sawadogo M., Roeder R. G. Energy requirement for specific transcription initiation by the human RNA polymerase II system. J Biol Chem. 1984 Apr 25;259(8):5321–5326. [PubMed] [Google Scholar]
- Schorpp M., Döbbeling U., Wagner U., Ryffel G. U. 5'-flanking and 5'-proximal exon regions of the two Xenopus albumin genes. Deletion analysis of constitutive promoter function. J Mol Biol. 1988 Jan 5;199(1):83–93. doi: 10.1016/0022-2836(88)90380-4. [DOI] [PubMed] [Google Scholar]
- Seiler-Tuyns A., Walker P., Martinez E., Mérillat A. M., Givel F., Wahli W. Identification of estrogen-responsive DNA sequences by transient expression experiments in a human breast cancer cell line. Nucleic Acids Res. 1986 Nov 25;14(22):8755–8770. doi: 10.1093/nar/14.22.8755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ulanovsky L., Bodner M., Trifonov E. N., Choder M. Curved DNA: design, synthesis, and circularization. Proc Natl Acad Sci U S A. 1986 Feb;83(4):862–866. doi: 10.1073/pnas.83.4.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wahli W., Ryffel G. U. Xenopus vitellogenin genes. Oxf Surv Eukaryot Genes. 1985;2:96–120. [PubMed] [Google Scholar]
- Walker P., Germond J. E., Brown-Luedi M., Givel F., Wahli W. Sequence homologies in the region preceding the transcription initiation site of the liver estrogen-responsive vitellogenin and apo-VLDLII genes. Nucleic Acids Res. 1984 Nov 26;12(22):8611–8626. doi: 10.1093/nar/12.22.8611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wu H. M., Crothers D. M. The locus of sequence-directed and protein-induced DNA bending. Nature. 1984 Apr 5;308(5959):509–513. doi: 10.1038/308509a0. [DOI] [PubMed] [Google Scholar]