Abstract
Transcriptional activation of the Xenopus laevis beta-globin gene requires the synergistic action of the simian virus 40 enhancer and DNA replication in DEAE-dextran-mediated HeLa cell transfections. Replication does not act through covalent modification of the template, since its requirement was not obviated by the prior replication of the transfected DNA in eucaryotic cells. Transfection of DNA over a 100-fold range demonstrates that replication does not contribute to gene activation simply increasing template copy number. Furthermore, in cotransfections of replicating and nonreplicating constructs, only replicating templates were transcribed. Replication is not simply a requirement of chromatin assembly, since even unreplicated templates generated nucleosomal ladders. Stimulation of beta-globin transcription by DNA replication, though less marked, was also observed in calcium phosphate transfections. We interpret these results as revealing a dynamic role for replication in gene activation.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
- Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
- Bendig M. M., Williams J. G. Differential expression of the Xenopus laevis tadpole and adult beta-globin genes when injected into fertilized Xenopus laevis eggs. Mol Cell Biol. 1984 Mar;4(3):567–570. doi: 10.1128/mcb.4.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bendig M. M., Williams J. G. Fidelity of transcription of Xenopus laevis globin genes injected into Xenopus laevis oocytes and unfertilized eggs. Mol Cell Biol. 1984 Oct;4(10):2109–2119. doi: 10.1128/mcb.4.10.2109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blow J. J., Laskey R. A. Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs. Cell. 1986 Nov 21;47(4):577–587. doi: 10.1016/0092-8674(86)90622-7. [DOI] [PubMed] [Google Scholar]
- Choi O. R., Engel J. D. A 3' enhancer is required for temporal and tissue-specific transcriptional activation of the chicken adult beta-globin gene. Nature. 1986 Oct 23;323(6090):731–734. doi: 10.1038/323731a0. [DOI] [PubMed] [Google Scholar]
- Cochran M. D., Weissmann C. Modular structure of the beta-globin and the TK promoters. EMBO J. 1984 Nov;3(11):2453–2459. doi: 10.1002/j.1460-2075.1984.tb02155.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crossland L. D., Raskas H. J. Identification of adenovirus genes that require template replication for expression. J Virol. 1983 Jun;46(3):737–748. doi: 10.1128/jvi.46.3.737-748.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devine J. M., Tsang A. S., Williams J. G. Differential expression of the members of the discoidin I multigene family during growth and development of Dictyostelium discoideum. Cell. 1982 Apr;28(4):793–800. doi: 10.1016/0092-8674(82)90058-7. [DOI] [PubMed] [Google Scholar]
- Dierks P., van Ooyen A., Cochran M. D., Dobkin C., Reiser J., Weissmann C. Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983 Mar;32(3):695–706. doi: 10.1016/0092-8674(83)90055-7. [DOI] [PubMed] [Google Scholar]
- Emerson B. M., Felsenfeld G. Specific factor conferring nuclease hypersensitivity at the 5' end of the chicken adult beta-globin gene. Proc Natl Acad Sci U S A. 1984 Jan;81(1):95–99. doi: 10.1073/pnas.81.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emerson B. M., Nickol J. M., Jackson P. D., Felsenfeld G. Analysis of the tissue-specific enhancer at the 3' end of the chicken adult beta-globin gene. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4786–4790. doi: 10.1073/pnas.84.14.4786. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enver T., Brewer A. C., Patient R. K. Simian virus 40-mediated cis induction of the Xenopus beta-globin DNase I hypersensitive site. Nature. 1985 Dec 19;318(6047):680–683. doi: 10.1038/318680a0. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
- Gilbert D. M. Temporal order of replication of Xenopus laevis 5S ribosomal RNA genes in somatic cells. Proc Natl Acad Sci U S A. 1986 May;83(9):2924–2928. doi: 10.1073/pnas.83.9.2924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
- Gluzman Y., Sambrook J. F., Frisque R. J. Expression of early genes of origin-defective mutants of simian virus 40. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3898–3902. doi: 10.1073/pnas.77.7.3898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldman M. A., Holmquist G. P., Gray M. C., Caston L. A., Nag A. Replication timing of genes and middle repetitive sequences. Science. 1984 May 18;224(4650):686–692. doi: 10.1126/science.6719109. [DOI] [PubMed] [Google Scholar]
- Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
- Grosveld G. C., de Boer E., Shewmaker C. K., Flavell R. A. DNA sequences necessary for transcription of the rabbit beta-globin gene in vivo. Nature. 1982 Jan 14;295(5845):120–126. doi: 10.1038/295120a0. [DOI] [PubMed] [Google Scholar]
- Guinta D. R., Korn L. J. Differential order of replication of Xenopus laevis 5S RNA genes. Mol Cell Biol. 1986 Jul;6(7):2536–2542. doi: 10.1128/mcb.6.7.2536. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hesse J. E., Nickol J. M., Lieber M. R., Felsenfeld G. Regulated gene expression in transfected primary chicken erythrocytes. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4312–4316. doi: 10.1073/pnas.83.12.4312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keller J. M., Alwine J. C. Analysis of an activatable promoter: sequences in the simian virus 40 late promoter required for T-antigen-mediated trans activation. Mol Cell Biol. 1985 Aug;5(8):1859–1869. doi: 10.1128/mcb.5.8.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kmiec E. B., Worcel A. The positive transcription factor of the 5S RNA gene induces a 5S DNA-specific gyration in Xenopus oocyte extracts. Cell. 1985 Jul;41(3):945–953. doi: 10.1016/s0092-8674(85)80075-1. [DOI] [PubMed] [Google Scholar]
- Kollias G., Hurst J., deBoer E., Grosveld F. The human beta-globin gene contains a downstream developmental specific enhancer. Nucleic Acids Res. 1987 Jul 24;15(14):5739–5747. doi: 10.1093/nar/15.14.5739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lebkowski J. S., Clancy S., Calos M. P. Simian virus 40 replication in adenovirus-transformed human cells antagonizes gene expression. Nature. 1985 Sep 12;317(6033):169–171. doi: 10.1038/317169a0. [DOI] [PubMed] [Google Scholar]
- Lewis E. D., Manley J. L. Repression of simian virus 40 early transcription by viral DNA replication in human 293 cells. Nature. 1985 Sep 12;317(6033):172–175. doi: 10.1038/317172a0. [DOI] [PubMed] [Google Scholar]
- Lund E., Bostock C. J., Dahlberg J. E. The transcription of Xenopus laevis embryonic U1 snRNA genes changes when oocytes mature into eggs. Genes Dev. 1987 Mar;1(1):47–56. doi: 10.1101/gad.1.1.47. [DOI] [PubMed] [Google Scholar]
- Lusky M., Berg L., Weiher H., Botchan M. Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit. Mol Cell Biol. 1983 Jun;3(6):1108–1122. doi: 10.1128/mcb.3.6.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Matsui T., Murayama M., Mita T. Adenovirus 2 peptide IX gene is expressed only on replicated DNA molecules. Mol Cell Biol. 1986 Dec;6(12):4149–4154. doi: 10.1128/mcb.6.12.4149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Myers R. M., Tilly K., Maniatis T. Fine structure genetic analysis of a beta-globin promoter. Science. 1986 May 2;232(4750):613–618. doi: 10.1126/science.3457470. [DOI] [PubMed] [Google Scholar]
- Patient R. K., Harris R., Walmsley M. E., Williams J. G. The complete nucleotide sequence of the major adult beta globin gene of Xenopus laevis. J Biol Chem. 1983 Jul 25;258(14):8521–8523. [PubMed] [Google Scholar]
- Seidman M. M., Levine A. J., Weintraub H. The asymmetric segregation of parental nucleosomes during chrosome replication. Cell. 1979 Oct;18(2):439–449. doi: 10.1016/0092-8674(79)90063-1. [DOI] [PubMed] [Google Scholar]
- Smithies O. The control of globin and other eukaryotic genes. J Cell Physiol Suppl. 1982;1:137–143. doi: 10.1002/jcp.1041130421. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Stillman B. Chromatin assembly during SV40 DNA replication in vitro. Cell. 1986 May 23;45(4):555–565. doi: 10.1016/0092-8674(86)90287-4. [DOI] [PubMed] [Google Scholar]
- TILL J. E., MCCULLOCH E. A., SIMINOVITCH L. A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. Proc Natl Acad Sci U S A. 1964 Jan;51:29–36. doi: 10.1073/pnas.51.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tegtmeyer P. Simian virus 40 deoxyribonucleic acid synthesis: the viral replicon. J Virol. 1972 Oct;10(4):591–598. doi: 10.1128/jvi.10.4.591-598.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas G. P., Mathews M. B. DNA replication and the early to late transition in adenovirus infection. Cell. 1980 Nov;22(2 Pt 2):523–533. doi: 10.1016/0092-8674(80)90362-1. [DOI] [PubMed] [Google Scholar]
- Treisman R., Green M. R., Maniatis T. cis and trans activation of globin gene transcription in transient assays. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7428–7432. doi: 10.1073/pnas.80.24.7428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Venkatesh L. K., Chinnadurai G. Activation of the adenovirus 2 protein IX promoter by DNA replication in a transient expression assay. Nucleic Acids Res. 1987 Mar 11;15(5):2235–2250. doi: 10.1093/nar/15.5.2235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wasylyk B., Wasylyk C., Augereau P., Chambon P. The SV40 72 bp repeat preferentially potentiates transcription starting from proximal natural or substitute promoter elements. Cell. 1983 Feb;32(2):503–514. doi: 10.1016/0092-8674(83)90470-1. [DOI] [PubMed] [Google Scholar]
- Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]