Methylation status and DNase I sensitivity of immunoglobulin genes: changes associated with rearrangement.
Immunoglobulin V kappa genes are transcriptionally silent in their germline context and become transcriptionally active upon fusion to the J kappa-C kappa region (kappa locus). To elucidate the role of chromosomal structure in this regulatory phenomenon we have investigated the DNase I sensitivity and methylation status of the kappa locus and selected V kappa genes in a variety of alleles exhibiting different rearrangement configurations and different levels of transcriptional activity. Our findings indicate that the kappa locus in either germline or rearranged contexts maintains a distinctive DNase I-sensitive, hypomethylated structure in plasmacytomas and hybridomas, irrespective of its level of transcriptional activity. In contrast, the germline V kappa genes are in less accessible regions of chromatin and more highly methylated regions of DNA. Upon fusion to the kappa locus, V kappa genes become DNase I-sensitive and hypomethylated. This effect extends several kilobases upstream of the transcriptional initiation site but does not extend to the adjacent V kappa gene or to the identical V kappa allele on the other chromosome, indicating that the structural alteration is a localized cis-acting phenomenon.
D000818:Animals; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics*; D002460:Cell Line; D004262:DNA Restriction Enzymes; D004273:DNA, Neoplasm / Q000302:isolation & purification; D003850:Deoxyribonuclease I; D004622:Embryo, Mammalian; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D005796:Genes; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008099:Liver / Q000276:immunology; D008745:Methylation; D051379:Mice; D009693:Nucleic Acid Hybridization; D010954:Plasmacytoma; D013379:Substrate Specificity
D004273:DNA, Neoplasm; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D004706:Endodeoxyribonucleases; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I