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A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13

Item Type:Article
Title:A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13
Creators Name:Valenza-Schaerly, P. and Pickard, B. and Walter, J. and Jung, M. and Pourcel, L. and Reik, W. and Gauguier, D. and Vergnaud, G. and Pourcel, C.
Abstract:The single-copy hepatitis B virus transgene in the E36 transgenic mouse strain undergoes methylation changes in a parent-of-origin, tissue, and strain-specific fashion. In a C57BL/6 background, the paternally transmitted transgene is methylated in 30% of cells, whereas it is methylated in more than 80% of cells in (BALB/c × C57BL/6) F1 mice. We established previously that several genetic factors were likely to contribute to the transgene methylation profile, some with demethylating and some with de novo methylating activities. Using quantitative trait loci (QTL) mapping, we have now localized one major modifier locus on chromosome 13 (Mod13), which explains a 30% increase in the methylation level of this transgene with no effect on the flanking endogenous sequences. No other QTL could be identified, except for a demethylating activity of low significance located on chromosome 12. Recombinant inbred mice containing a BALB/c allele of Mod13 were then used to show that the presence of Mod13 is sufficient to induce de novo methylation. A segregation between de novo methylation and repression of transgene expression was uncovered, suggesting that this genetic system is also useful for the identification of factors that interpret methylation patterns in the genome.
Keywords:Chromosome Mapping, DNA Methylation, Genetic Crosses, Genetic Markers, Genetic Recombination, Heritable Quantitative Trait, Inbred BALB C Mice, Inbred C57BL Mice, Liver, Lung, Multifactorial Inheritance, Myocardium, Newborn Animals, Transgenic Mice, Transgenes, Animals, Mice
Source:Genome Research
ISSN:1088-9051
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:11
Number:3
Page Range:382-388
Date:1 January 2001
Official Publication:https://doi.org/10.1101/gr.163801
PubMed:View item in PubMed

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