The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle
Abstract
Background: Although the transient nature of transgene expression using first‐generation adenovirus (Ad) vectors is well known, the exact mechanisms responsible for this phenomenon are uncertain. Methods: Rats were given intramuscular (i.m.) injections of a first‐generation Ad containing the human fibroblast growth factor 4 (hFGF‐4) gene driven by the cytomegalovirus (CMV) promoter and enhancer (CMV‐PE). The copy number of hFGF‐4 mRNA and viral DNA was measured in the same muscles by quantitative RT‐PCR and quantitative PCR at times between 1 h and 84 days after virus injection. Quantitative Southern blot analysis for the intact hFGF‐4 transcription unit DNA was also performed, and the methylation status of the CMV‐PE DNA in the muscle was determined using bisulfite sequencing. Results: The copy number of hFGF‐4 mRNA peaked at 6 h then decreased 56‐fold by 24 h, and a further 240‐fold between days 3 and 28. Although the viral DNA copy number also decreased 23‐fold between 6 h and 28 days, the ratio of copies of hFGF‐4 mRNA per copy of viral DNA decreased 385‐fold over this period. Methylation of the CMV‐PE DNA in the muscle at both CpG and non‐CpG sites was observed 24 h after virus administration and had increased at day 7. Conclusions: Decreased transcription associated with extensive methylation of the CMV‐PE was the major mechanism responsible for the decrease in transgene mRNA levels. Strategies for preventing transcriptional silencing will be valuable for improving the duration of transgene expression from adenoviral vectors. Copyright © 2004 John Wiley & Sons, Ltd.
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DNA methylation in health and disease
Robertson, K. D., & Wolffe, A. P. (2000) · Nature Reviews Genetics · doi:10.1038/35049533 · Cited by 1,057
Ramsahoye, B. H., Biniszkiewicz, D., Lyko, F., Clark, V., Bird, A. P., & Jaenisch, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5237 · Cited by 970
Dai, Y., Schwarz, E. M., Gu, D., Zhang, W. W., Sarvetnick, N., & Verma, I. M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.5.1401 · Cited by 591
Duan, D., Sharma, P., Yang, J., Yue, Y., Dudus, L., Zhang, Y., Fisher, K. J., & Engelhardt, J. F. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8568-8577.1998 · Cited by 522
Fallaux, F. J., Bout, A., van der Velde, I., van den Wollenberg, D. J. M., Hehir, K. M., Keegan, J., Auger, C., Cramer, S. J., van Ormondt, H., van der Eb, A. J., et al. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.13-1909 · Cited by 479
Hypermethylated SUPERMAN Epigenetic Alleles in Arabidopsis
Jacobsen, S. E., & Meyerowitz, E. M. (1997) · Science · doi:10.1126/science.277.5329.1100 · Cited by 434
Methyl‐CpG‐binding proteins: Targeting specific gene repression
Ballestar, E., & Wolffe, A. P. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.01869.x · Cited by 408
White, G. P., Watt, P. M., Holt, B. J., & Holt, P. G. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.6.2820 · Cited by 328
Qin, L., Ding, Y., Pahud, D. R., Chang, E., Imperiale, M. J., & Bromberg, J. S. (1997) · Human Gene Therapy · doi:10.1089/hum.1997.8.17-2019 · Cited by 315
Sutter, D., & Doerfler, W. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.1.253 · Cited by 298
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Zode, G. S., Kuehn, M. H., Nishimura, D. Y., Searby, C. C., Mohan, K., Grozdanic, S. D., Bugge, K., Anderson, M. G., Clark, A. F., Stone, E. M., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58183 · Cited by 268
Efficient Non-Viral Ocular Gene Transfer with Compacted DNA Nanoparticles
Farjo, R., Skaggs, J., Quiambao, A. B., Cooper, M. J., & Naash, M. I. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000038 · Cited by 208
Next-generation AAV vectors—Do not judge a virus (only) by its cover
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Metadata
- Authors
- Brooks, A. R., Harkins, R. N., Wang, P., Qian, H. S., Liu, P., & Rubanyi, G. M.
- Venue
- The Journal of Gene Medicine
- Publisher
- Wiley
- Published
- 2004-02-10
- Volume
- 6
- Issue
- 4
- Pages
- 395-404
- ISSN
- 1099-498X (ISSN-L)
- 1521-2254
- OpenAlex
- W2039618053
- Cited by
- 362
- References
- 22
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- closed
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- Brooks, A. R., Harkins, R. N., Wang, P., Qian, H. S., Liu, P., & Rubanyi, G. M. (2004). Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle. The Journal of Gene Medicine. https://doi.org/10.1002/jgm.516
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