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

Abstract

DNase I as a probe to examine the chromatin structure of mouse Ig .kappa. L 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 1 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. During the development of B lymphocytes, the commitment of Ig .kappa. L 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. 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 Ig 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. The DNase I-hypersensitive sites in the J.kappa.-C.kappa. intron region are not associated with any known promoters. 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 SV40, which was 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.