A ROLE FOR NUCLEAR NF-KB IN B-CELL SPECIFIC DEMETHYLATION OF THE IG-KAPPA LOCUS

The immunoglobulin kappa gene is specifically demethylated during B-ce ll maturation in a process which utilizes discrete cis-acting modules such as the intronic kappa enhancer element and the matrix attachment region (MAR). While any MAR sequence is sufficient for this reaction, mutation analysis indicates that tissue specificity is mediated by kap pa B binding sequences within the kappa intronic enhancer. The plasmac ytoma cell line S107 lacks kappa B binding activity and fails to demet hylate the kappa locus. However, B-cell-specific demethylation is rest ored by the introduction of an active kappa B binding protein gene, re lB. This represents the first demonstration of a trans-acting factor i nvolved in cell-type-specific demethylation, and suggests that the sam e protein-DNA recognition system used for transcription may also contr ibute to the earlier developmental events that bring about activation of the kappa locus.