The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Repeat-induced gene silencing in mammals
Abstract
In both plants and Drosophila melanogaster, expression from a transgenic locus may be silenced when repeated transgene copies are arranged as a concatameric array. This repeat-induced gene silencing is frequently manifested as a decrease in the proportion of cells that express the transgene, resulting in a variegated pattern of expression. There is also some indication that, in transgenic mammals, the number of transgene copies within an array can exert a repressive influence on expression, with several mouse studies reporting a decrease in the level of expression per copy as copy number increases. However, because these studies compare different sites of transgene integration as well as arrays with different numbers of copies, the expression levels observed may be subject to varying position effects as well as the influence of the multicopy array. Here we describe use of the lox/Cre system of site-specific recombination to generate transgenic mouse lines in which different numbers of a transgene are present at the same chromosomal location, thereby eliminating the contribution of position effects and allowing analysis of the effect of copy number alone on transgene silencing. Reduction in copy number results in a marked increase in expression of the transgene and is accompanied by decreased chromatin compaction and decreased methylation at the transgene locus. These findings establish that the presence of multiple homologous copies of a transgene within a concatameric array can have a repressive effect upon gene expression in mammalian systems.
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In the citing paper
“This site of integration is neither centromeric nor telomeric, and so presumably the silencing is related to the multicopy nature of the transgene array [13,14].”
From A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development (2008) · cites this paper as [13]
In the citing paper
“transgene silencing,4”
From Adeno‐associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo†‡ (2010) · cites this paper as [4]
Citations
Cites
Position-independent, high-level expression of the human β-globin gene in transgenic mice
Grosveld, F. G., van Assendelft, G. B., Greaves, D. R., & Kollias, G. A. (1987) · Cell · doi:10.1016/0092-8674(87)90584-8 · Cited by 1,908
GERM-LINE TRANSFORMATION OF MICE
Palmiter, R. D., & Brinster, R. L. (1986) · Annual Review of Genetics · doi:10.1146/annurev.ge.20.120186.002341 · Cited by 1,157
Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
Lakso, M., Pichel, J. G., Gorman, J. R., Sauer, B., Okamoto, Y., Lee, E., Alt, F. W., & Westphal, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5860 · Cited by 1,125
Reversible methylation and inactivation of marker genes in sequentially transformed tobacco plants
Matzke, M. A., Primig, M., Trnovsky, J., & Matzke, A. J. M. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03421.x · Cited by 545
Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila
Dorer, D. R. (1994) · Cell · doi:10.1016/0092-8674(94)90439-1 · Cited by 504
The basics of basal transcription by RNA polymerase II
Buratowski, S. (1994) · Cell · doi:10.1016/0092-8674(94)90226-7 · Cited by 410
A major positive regulatory region located far upstream of the human alpha-globin gene locus.Preprint
Higgs, D. R., Wood, W. G., Jarman, A. P., Sharpe, J. A., Lida, J., Pretorius, I., & Ayyub, H. (1990) · Genes & Development · doi:10.1101/gad.4.9.1588 · Cited by 335
Suppression of beta‐1,3‐glucanase transgene expression in homozygous plants.
de Carvalho‐Niebel, F., Gheysen, G., Kushnir, S., MONTAGU, M. V., Inzé, D., & Castresana, C. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05324.x · Cited by 304
Araki, K., Araki, M., Miyazaki, J., & VASSALLI, P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.1.160 · Cited by 284
Linne, F., Heidmann, I., Saedler, H., & Meyer, P. (1990) · Molecular and General Genetics MGG · doi:10.1007/bf00633837 · Cited by 281
Cited by
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DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
“The most suggestive evidence in mammals concerns manipulation of transgene copy number at a single locus in the mouse genome using cre-lox technology (Garrick et al. 1998).”
MethodComplement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP
Feng, G., Mellor, R. H., Bernstein, M., Keller-Peck, C., Nguyen, Q. T., Wallace, M., Nerbonne, J. M., Lichtman, J. W., & Sanes, J. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00084-2 · Cited by 3,042
Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system
Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., Sanes, J. R., & Lichtman, J. W. (2007) · Nature · doi:10.1038/nature06293 · Cited by 1,876
Methylation-Induced Repression— Belts, Braces, and Chromatin
Bird, A. P., & Wolffe, A. P. (1999) · Cell · doi:10.1016/s0092-8674(00)81532-9 · Cited by 1,858
Metadata
- Authors
- Garrick, D., Fiering, S., Martin, D. I. K., & Whitelaw, E.
- Affiliations
- The University of Sydney (AU)
- Dartmouth–Hitchcock Medical Center (US)
- Fred Hutch Cancer Center (US)
- Venue
- Nature Genetics
- Published
- 1998-01
- Volume
- 18
- Issue
- 1
- Pages
- 56-59
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2065189089
- Cited by
- 887
- References
- 32
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 20 · 2023: 16 · 2022: 9 · 2021: 16 · 2020: 16 · 2019: 14 · 2018: 20 · 2017: 23 · 2016: 25 · 2015: 28 · 2014: 24 · 2013: 24 · 2012: 41
- FWCI
- 36.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- transgene copy number, transgene silencing, position effect, transgenic mice, chromatin condensation, DNA methylation, epigenetic silencing
- MeSH terms
- Animals, Chromatin, Erythrocytes, Female, Gene Expression Regulation, Humans, Lac Operon, Male, Mammals, Mice, Transgenic, Repetitive Sequences, Nucleic Acid, Transcription, Genetic, Viral Proteins, Gene Dosage, Transgenes, Integrases, Mice
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