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

Pascale Valenza-Schaerly, Benjamin Pickard, Jörn Walter, Martin Jung, Lucille Pourcel, Wolf Reik, Dominique Gauguier, Gilles Vergnaud, Christine Pourcel

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 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.
LanguageEnglish
Pages382-388
Number of pages7
JournalGenome Research
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2001

Fingerprint

Chromosomes, Human, Pair 13
Quantitative Trait Loci
Transgenes
Methylation
Chromosomes, Human, Pair 12
Hepatitis B virus
Transgenic Mice
Alleles
Genome

Keywords

  • heritable recombination
  • newborns
  • genetics
  • chromosome mapping
  • metabolism
  • liver disease
  • Hepatitis B

Cite this

Valenza-Schaerly, P., Pickard, B., Walter, J., Jung, M., Pourcel, L., Reik, W., ... Pourcel, C. (2001). A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13. Genome Research, 11(3), 382-388. https://doi.org/10.1101/gr.163801
Valenza-Schaerly, Pascale ; Pickard, Benjamin ; Walter, Jörn ; Jung, Martin ; Pourcel, Lucille ; Reik, Wolf ; Gauguier, Dominique ; Vergnaud, Gilles ; Pourcel, Christine. / A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13. In: Genome Research. 2001 ; Vol. 11, No. 3. pp. 382-388.
@article{46e8d8a208e24bcea2d34ef01ede5f1e,
title = "A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13",
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 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.",
keywords = "heritable recombination, newborns, genetics, chromosome mapping, metabolism, liver disease, Hepatitis B",
author = "Pascale Valenza-Schaerly and Benjamin Pickard and J{\"o}rn Walter and Martin Jung and Lucille Pourcel and Wolf Reik and Dominique Gauguier and Gilles Vergnaud and Christine Pourcel",
year = "2001",
month = "3",
doi = "10.1101/gr.163801",
language = "English",
volume = "11",
pages = "382--388",
journal = "Genome Research",
issn = "1088-9051",
number = "3",

}

Valenza-Schaerly, P, Pickard, B, Walter, J, Jung, M, Pourcel, L, Reik, W, Gauguier, D, Vergnaud, G & Pourcel, C 2001, 'A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13' Genome Research, vol. 11, no. 3, pp. 382-388. https://doi.org/10.1101/gr.163801

A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13. / Valenza-Schaerly, Pascale; Pickard, Benjamin; Walter, Jörn; Jung, Martin; Pourcel, Lucille; Reik, Wolf; Gauguier, Dominique; Vergnaud, Gilles; Pourcel, Christine.

In: Genome Research, Vol. 11, No. 3, 03.2001, p. 382-388.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A dominant modifier of transgene methylation is mapped by QTL analysis to mouse chromosome 13

AU - Valenza-Schaerly, Pascale

AU - Pickard, Benjamin

AU - Walter, Jörn

AU - Jung, Martin

AU - Pourcel, Lucille

AU - Reik, Wolf

AU - Gauguier, Dominique

AU - Vergnaud, Gilles

AU - Pourcel, Christine

PY - 2001/3

Y1 - 2001/3

N2 - 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.

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.

KW - heritable recombination

KW - newborns

KW - genetics

KW - chromosome mapping

KW - metabolism

KW - liver disease

KW - Hepatitis B

UR - http://genome.cshlp.org/

U2 - 10.1101/gr.163801

DO - 10.1101/gr.163801

M3 - Article

VL - 11

SP - 382

EP - 388

JO - Genome Research

T2 - Genome Research

JF - Genome Research

SN - 1088-9051

IS - 3

ER -