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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“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]
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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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