Methylation status of immunoglobulin kappa gene segments correlates with their recombination potential.
We have previously shown that unlike endogenous chi genes, unrearranged chi transgenes undergo V chi-J chi recombination in Tas well as B cells of transgenic mice. To determine whether the difference in recombination specificity of the transgenic and endogenous chi genes is associated with differences in DNA structure, the methylation status of the endogenous genes and three unrearranged chi transgenes was compared. The J chi-C chi locus of the transgenes was found to be hypomethylated in all tissues of the transgenic mice. In contrast, methylation of the endogenous chi genes was tissue and developmentally regulated. Hypomethylation of the endogenous J chi-C chi region occurs only in cells of the B lineage undergoing, or having completed chi 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 chi genes. These results suggest that hypomethylation defines an accessible state of the chi locus and that methylation/demethylation could be involved in the control of chi gene rearrangement during lymphocyte differentiation.
Goodhardt
M
M
Unité de Génetique et Biochimie du Dévelopement, Institut Pasteur, Paris, France.
Cavelier
P
P
Doyen
N
N
Kallenbach
S
S
Babinet
C
C
Rougeon
F
F
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D018398:Homeodomain Proteins; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007127:Immunoglobulin Constant Regions; D007133:Immunoglobulin Joining Region; D007145:Immunoglobulin kappa-Chains; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein