Open AccessInfluence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate.
Author(s) -
Peter Engler,
Andrew P. Weng,
Ursula Storb
Publication year - 1993
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.13.1.571
Subject(s) - biology , transgene , recombination , recombinase , cre recombinase , cpg site , v(d)j recombination , methylation , microbiology and biotechnology , site specific recombination , flp frt recombination , genetically modified mouse , mitotic crossover , ectopic recombination , dna methylation , dna , gene , genetics , genetic recombination , gene expression
We have previously described a line of transgenic mice with multiple head-to-tail copies of an artificial V-J recombination substrate and have shown that the methylation of this transgene is under the control of a dominant strain-specific modifier gene, Ssm-1. When the transgene array is highly methylated, no recombination is detectable, but when it is unmethylated, V-J joining is seen in the spleen, bone marrow, lymph nodes, and Peyer's patches but not in the thymus or nonlymphoid tissues, including brain tissue. Strikingly, in mice with partially methylated transgene arrays, rearrangement preferentially occurs in hypomethylated copies. Therefore, V-J recombination is negatively correlated with methylated DNA sequences. In addition, it appears that recombination occurs randomly between any two recombination signal sequences within the transgene array. This lack of target preference in an unselectable array of identical targets rules out simple mechanisms of one-dimensional tracking of a V(D)J recombinase complex.