DNase I-hypersensitive sites in the chromatin of immunoglobulin kappa light chain genes.

We have used DNase I as a probe to examine the chromatin structure of mouse immunoglobulin kappa light chain genes in rearranged and unrearranged chromosomes--i.e., in nuclei from myeloma cells and from brain and liver cells. Tissue-specific DNase I-hypersensitive sites are observed 0.7 and 1.7 kilobases upstream from the 5' end of the C kappa gene in the J kappa -C kappa intron region in myeloma nuclei but not in naked DNA or in brain or liver nuclei. In myeloma cells expressing one functional kappa light chain polypeptide, but with more than one rearranged allele, one DNase I-hypersensitive site is found 0.3 kilobases upstream from the start of the coding region of the V kappa sequence in both functionally rearranged and nonfunctionally rearranged alleles but not in cross-hybridizing V kappa genes in the germ line context. Thus, during the development of B lymphocytes, the commitment of immunoglobulin kappa light chain gene expression seems to be associated with the presence of DNase I hypersensitivities that reflect changes of chromosomal structure surrounding the single copy C kappa gene. In contrast, the germ line V kappa multigene family seems to be located in a chromosomal region that does not exhibit change of DNase I hypersensitivity in response to commitment of immunoglobulin expression; a V kappa gene acquires DNase I hypersensitivity only after it is translocated adjacent to the J kappa -C kappa intron region. The DNase I-hypersensitive site 5' to the V kappa sequence is similar in location to hypersensitive sites found for other eukaryotic genes and is probably associated with the promoter region. However, the DNase I-hypersensitive sites in the J kappa -C kappa intron region are not associated with any known promoters. In addition, the DNA sequences surrounding the C kappa-proximal DNase I-hypersensitive site have several stretches of homology with sequences within the 72-base-pair tandem repeat of simian virus 40, which has been shown to modulate the transcriptional activity of neighboring genes. This DNase I-hypersensitive site in the intron region may be significant for the differential expression of the translocated V kappa genes.