Methylation status of immunoglobulin x e segments correlates with their recombination potential

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Abstract
We have previously shown that unlike endogenous ϰ genes, unrearranged ϰ transgenes undergo Vϰ‐Jϰ recombination in T as well as B cells of transgenic mice. To determine whether the difference in recombination specificity of the transgenic and endogenous ϰ genes is associated with differences in DNA structure, the methylation status of the endogenous genes and three unrearranged ϰ transgenes was compared. The Jϰ‐Cϰ locus of the transgenes was found to be hypomethylated in all tissues of the transgenic mice. In contrast, methylation of the endogenous ϰ genes was tissue and developmentally regulated. Hypomethylation of the endogenous Jϰ‐Cϰ region occurs only in cells of the B lineage undergoing, or having completed ϰ gene recombination. Transfection of fibroblasts from transgenic and control mice with the recombination activating genes, Rag1 and Rag2, led to a high level of rearrangement of the hypomethylated transgenic, but not the endogenous ϰ genes. These results suggest that hypomethylation defines an accessible state of the ϰ locus and that methylation/demethylation could be involved in the control of ϰ gene rearrangement during lymphocyte differentiation.