M. Goodhardt et al., METHYLATION STATUS OF IMMUNOGLOBULIN CHI GENE SEGMENTS CORRELATES WITH THEIR RECOMBINATION POTENTIAL, European Journal of Immunology, 23(8), 1993, pp. 1789-1795
We have previously shown that unlike endogenous kappa genes, unrearran
ged kappa transgenes undergo Vkappa-Jkappa recombination in T as well
as B cells of transgenic mice. To determine whether the difference in
recombination specificity of the transgenic and endogenous kappa genes
is associated with differences in DNA structure, the methylation stat
us of the endogenous genes and three unrearranged kappa transgenes was
compared. The Jkappa-Ckappa locus of the transgenes was found to be h
ypomethylated in all tissues of the transgenic mice. In contrast, meth
ylation of the endogenous kappa genes was tissue and developmentally r
egulated. Hypomethylation of the endogenous Jkappa-Ckappa region occur
s only in cells of the B lineage undergoing, or having completed kappa
gene recombination. Transfection of fibroblasts from transgenic and c
ontrol mice with the recombination activating genes, Rag1 and Rag2, le
d to a high level of rearrangement of the hypomethylated transgenic, b
ut not the endogenous kappa genes. These results suggest that hypometh
ylation defines an accessible state of the kappa locus and that methyl
ation/demethylation could be involved in the control of kappa gene rea
rrangement during lymphocyte differentiation.