Structure of a nuclease-sensitive region inside the immunoglobin kappa gene: evidence for a role in gene regulation.

A discrete chromatin region inside the active immunoglobulin kappa gene is preferentially accessible to cleavage by nucleolytic enzymes. This region comprises 200-250 bp of DNA, and is situated within the large intron of the gene, approximately 600 bp upstream from the constant region coding sequence. The local chromatin structure of this region correlates with tissue-specific kappa gene expression: it is resistant to nucleolytic digestion in the inactive kappa genes of murine brain and liver nuclei, but becomes uniquely sensitive to cleavage by deoxyribonuclease I or by a variety of restriction endonucleases in the chromatin of kappa-producing cells. Nuclease sensitivity at this site occurs in both rearranged and unrearranged kappa alleles, and can be maintained in the absence of ongoing kappa transcription. The nucleotide sequence of the hypersensitive region has been selectively conserved in evolution, and includes both a 7 bp inverted repeat sequence and a short segment homologous to the transcriptional enhancer elements of certain eukaryotic viruses. Molecular events occurring at this locus may play a role in the regulation of kappa gene expression, perhaps by influencing the activity of promoter sequences several kilobases upstream.