RT Journal
A1 Valenza-Schaerly, Pascale
A1 Pickard, Benjamin
A1 Walter, Jörn
A1 Jung, Martin
A1 Pourcel, Lucille
A1 Reik, Wolf
A1 Gauguier, Dominique
A1 Vergnaud, Gilles
A1 Pourcel, Christine
T1 A Dominant Modifier of Transgene Methylation Is Mapped by QTL Analysis to Mouse Chromosome 13
JF Genome Research 
JO Genome Research 
YR 2001 
FD March 01 
VO 11 
IS 3 
SP 382 
OP 388 
DO 10.1101/gr.163801 
UL http://genome.cshlp.org/content/11/3/382.abstract 
AB 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 x 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.