Methylation status and DNase I sensitivity of immunoglobulin genes: changes associated with rearrangement.

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Abstract
Ig V.kappa. genes are transcriptionally silent in their germline context and become transcriptionally active upon fusion of the J.kappa.-C.kappa. region (.kappa. locus). To elucidate the role of chromosomal structure in this regulatory phenomenon the DNase I sensitivity and methylation status of the .kappa. locus and selected V.kappa. genes was investigated in a variety of alleles exhibiting different rearrangement configurations and different levels of transcriptional activity. Apparently, the .kappa. locus in either germline or rearranged contexts maintains a distinctive DNase I-sensitive, hypomethylated structure in [mouse] 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.