Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate.

AUTOR(ES)

Engler, P

RESUMO

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.

Documentos Relacionados

• CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication.
• Sequences affecting the V(D)J recombinational activity of the IgH intronic enhancer in a transgenic substrate.
• A V(D)J recombinase-inducible B-cell line: role of transcriptional enhancer elements in directing V(D)J recombination.
• Mechanistic constraints on diversity in human V(D)J recombination.
• Both V(D)J recombination and radioresistance require DNA-PK kinase activity, though minimal levels suffice for V(D)J recombination