This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Challita, P. M. Articles by Kohn, D. B. Search for Related Content PubMed PubMed Citation Articles by Challita, P. M. Articles by Kohn, D. B.

 Previous Article  |  Next Article 

J. Virol., 02 1995, 748-755, Vol 69, No. 2
Copyright © 1995, American Society for Microbiology

Multiple modifications in cis elements of the long terminal repeat of retroviral vectors lead to increased expression and decreased DNA methylation in embryonic carcinoma cells

PM Challita, D Skelton, A el-Khoueiry, XJ Yu, K Weinberg and DB Kohn
Department of Microbiology, University of Southern California School of Medicine, Los Angeles.

Infection by murine retroviruses in embryonic carcinoma (EC) and embryonic stem cells is highly restricted. The transcriptional unit of the Moloney murine leukemic virus (MoMuLV) long terminal repeat (LTR) is inactive in EC and embryonic stem cells in association with increased proviral methylation. In this study, expression in F9 EC cells was achieved from novel retroviral vectors containing three modifications in the MoMuLV-based retroviral vector: presence of the myeloproliferative sarcoma virus LTR, substitution of the primer binding site, and either deletion of a negative control region at the 5' end of the LTR or insertion of a demethylating sequence. We conclude that inhibition of expression from the MoMuLV LTR in EC cells is mediated through the additive effects of multiple cis-acting elements affecting the state of methylation of the provirus.

This article has been cited by other articles:

• Senigl, F., Plachy, J., Hejnar, J. (2008). The Core Element of a CpG Island Protects Avian Sarcoma and Leukosis Virus-Derived Vectors from Transcriptional Silencing. J. Virol. 82: 7818-7827 [Abstract] [Full Text]  
• Hendrickson, B., Senadheera, D., Mishra, S., Bui, K. C. T., Wang, X., Chan, B., Petersen, D., Pepper, K., Lutzko, C. (2007). Development of Lentiviral Vectors with Regulated Respiratory Epithelial Expression In Vivo. Am. J. Respir. Cell Mol. Bio. 37: 414-423 [Abstract] [Full Text]  
• Koch, P., Siemen, H., Biegler, A., Itskovitz-Eldor, J., Brustle, O. (2006). Transduction of human embryonic stem cells by ecotropic retroviral vectors. Nucleic Acids Res 34: e120-e120 [Abstract] [Full Text]  
• Van Damme, A., Thorrez, L., Ma, L., Vandenburgh, H., Eyckmans, J., Dell'Accio, F., De Bari, C., Luyten, F., Lillicrap, D., Collen, D., VandenDriessche, T., Chuah, M. K.L. (2006). Efficient Lentiviral Transduction and Improved Engraftment of Human Bone Marrow Mesenchymal Cells. Stem Cells 24: 896-907 [Abstract] [Full Text]  
• Bartlett, D. W., Davis, M. E. (2006). Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic Acids Res 34: 322-333 [Abstract] [Full Text]  
• He, J., Yang, Q., Chang, L.-J. (2005). Dynamic DNA Methylation and Histone Modifications Contribute to Lentiviral Transgene Silencing in Murine Embryonic Carcinoma Cells. J. Virol. 79: 13497-13508 [Abstract] [Full Text]  
• Hu-Lieskovan, S., Heidel, J. D., Bartlett, D. W., Davis, M. E., Triche, T. J. (2005). Sequence-Specific Knockdown of EWS-FLI1 by Targeted, Nonviral Delivery of Small Interfering RNA Inhibits Tumor Growth in a Murine Model of Metastatic Ewing's Sarcoma. Cancer Res. 65: 8984-8992 [Abstract] [Full Text]  
• Wang, X., Rosol, M., Ge, S., Peterson, D., McNamara, G., Pollack, H., Kohn, D. B., Nelson, M. D., Crooks, G. M. (2003). Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging. Blood 102: 3478-3482 [Abstract] [Full Text]  
• Kurre, P., Morris, J., Thomasson, B., Kohn, D. B., Kiem, H.-P. (2003). Scaffold attachment region-containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells. Blood 102: 3117-3119 [Abstract] [Full Text]  
• Yao, S., Osborne, C. S., Bharadwaj, R. R., Pasceri, P., Sukonnik, T., Pannell, D., Recillas-Targa, F., West, A. G., Ellis, J. (2003). Retrovirus silencer blocking by the cHS4 insulator is CTCF independent. Nucleic Acids Res 31: 5317-5323 [Abstract] [Full Text]  
• Haas, D. L., Lutzko, C., Logan, A. C., Cho, G. J., Skelton, D., Jin Yu, X., Pepper, K. A., Kohn, D. B. (2003). The Moloney Murine Leukemia Virus Repressor Binding Site Represses Expression in Murine and Human Hematopoietic Stem Cells. J. Virol. 77: 9439-9450 [Abstract] [Full Text]  
• Lutzko, C., Senadheera, D., Skelton, D., Petersen, D., Kohn, D. B. (2003). Lentivirus Vectors Incorporating the Immunoglobulin Heavy Chain Enhancer and Matrix Attachment Regions Provide Position-Independent Expression in B Lymphocytes. J. Virol. 77: 7341-7351 [Abstract] [Full Text]  
• Grove, J. E., Lutzko, C., Priller, J., Henegariu, O., Theise, N. D., Kohn, D. B., Krause, D. S. (2002). Marrow-Derived Cells as Vehicles for Delivery of Gene Therapy to Pulmonary Epithelium. Am. J. Respir. Cell Mol. Bio. 27: 645-651 [Abstract] [Full Text]  
• Zaiss, A.-K., Son, S., Chang, L.-J. (2002). RNA 3' Readthrough of Oncoretrovirus and Lentivirus: Implications for Vector Safety and Efficacy. J. Virol. 76: 7209-7219 [Abstract] [Full Text]  
• Modin, C., Pedersen, F. S., Duch, M. (2000). Lack of Shielding of Primer Binding Site Silencer-Mediated Repression of an Internal Promoter in a Retrovirus Vector by the Putative Insulators scs, BEAD-1, and HS4. J. Virol. 74: 11697-11707 [Abstract] [Full Text]  
• Rivella, S., Callegari, J. A., May, C., Tan, C. W., Sadelain, M. (2000). The cHS4 Insulator Increases the Probability of Retroviral Expression at Random Chromosomal Integration Sites. J. Virol. 74: 4679-4687 [Abstract] [Full Text]  
• Persons, D. A., Nienhuis, A. W. (2000). Gene therapy for the hemoglobin disorders: Past, present, and future. Proc. Natl. Acad. Sci. USA 97: 5022-5024 [Full Text]  
• Young, W.-B., Lindberg, G. L., Link, C. J. Jr. (2000). DNA Methylation of Helper Virus Increases Genetic Instability of Retroviral Vector Producer Cells. J. Virol. 74: 3177-3187 [Abstract] [Full Text]  
• Dang, Q., Auten, J., Plavec, I. (2000). Human Beta Interferon Scaffold Attachment Region Inhibits De Novo Methylation and Confers Long-Term, Copy Number-Dependent Expression to a Retroviral Vector. J. Virol. 74: 2671-2678 [Abstract] [Full Text]  
• Donahue, R. E., Wersto, R. P., Allay, J. A., Agricola, B. A., Metzger, M. E., Nienhuis, A. W., Persons, D. A., Sorrentino, B. P. (2000). High levels of lymphoid expression of enhanced green fluorescent protein in nonhuman primates transplanted with cytokine-mobilized peripheral blood CD34+ cells. Blood 95: 445-452 [Abstract] [Full Text]  
• Williams, D. A., Nienhuis, A. W., Hawley, R. G., Smith, F. O. (2000). Gene Therapy 2000. ASH Education Book 2000: 376-393 [Abstract] [Full Text]  
• Halene, S., Wang, L., Cooper, R. M., Bockstoce, D. C., Robbins, P. B., Kohn, D. B. (1999). Improved Expression in Hematopoietic and Lymphoid Cells in Mice After Transplantation of Bone Marrow Transduced With a Modified Retroviral Vector. Blood 94: 3349-3357 [Abstract] [Full Text]  
• Osborne, C. S., Pasceri, P., Singal, R., Sukonnik, T., Ginder, G. D., Ellis, J. (1999). Amelioration of Retroviral Vector Silencing in Locus Control Region beta -Globin-Transgenic Mice and Transduced F9 Embryonic Cells. J. Virol. 73: 5490-5496 [Abstract] [Full Text]  
• Ramchandani, S., Bhattacharya, S. K., Cervoni, N., Szyf, M. (1999). DNA methylation is a reversible biological signal. Proc. Natl. Acad. Sci. USA 96: 6107-6112 [Abstract] [Full Text]  
• Zhang, P., Iwama, A., Datta, M. W., Darlington, G. J., Link, D. C., Tenen, D. G. (1998). Upregulation of Interleukin 6 and Granulocyte Colony-Stimulating Factor Receptors by Transcription Factor CCAAT Enhancer Binding Protein alpha  (C/EBPalpha ) Is Critical for Granulopoiesis. J. Exp. Med. 188: 1173-1184 [Abstract] [Full Text]  
• Robbins, P. B., Skelton, D. C., Yu, X.-J., Halene, S., Leonard, E. H., Kohn, D. B. (1998). Consistent, persistent expression from modified retroviral vectors in murine hematopoietic stem cells. Proc. Natl. Acad. Sci. USA 95: 10182-10187 [Abstract] [Full Text]  
• Jacob, J., Haug, J. S., Raptis, S., Link, D. C. (1998). Specific Signals Generated by the Cytoplasmic Domain of the Granulocyte Colony-Stimulating Factor (G-CSF) Receptor Are Not Required for G-CSF-Dependent Granulocytic Differentiation. Blood 92: 353-361 [Abstract] [Full Text]  
• Laker, C., Meyer, J., Schopen, A., Friel, J., Heberlein, C., Ostertag, W., Stocking, C. (1998). Host cis-Mediated Extinction of a Retrovirus Permissive for Expression in Embryonal Stem Cells during Differentiation. J. Virol. 72: 339-348 [Abstract] [Full Text]  
• Lengauer, C., Kinzler, K. W., Vogelstein, B. (1997). DNA methylation and genetic instability in colorectal cancer cells. Proc. Natl. Acad. Sci. USA 94: 2545-2550 [Abstract] [Full Text]  
• Dao, M. A., Hannum, C. H., Kohn, D. B., Nolta, J. A. (1997). FLT3 Ligand Preserves the Ability of Human CD34+ Progenitors to Sustain Long-Term Hematopoiesis in Immune-Deficient Mice After Ex Vivo Retroviral-Mediated Transduction. Blood 89: 446-456 [Abstract] [Full Text]