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-cell 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 kappa B binding sequences within the kappa intronic enhancer. The plasmacytoma cell line S107 lacks kappa B binding activity and fails to demethylate the kappa locus. However, B-cell-specific demethylation is restored by the introduction of an active kappa B binding protein gene, relB. This represents the first demonstration of a trans-acting factor involved in cell-type-specific demethylation, and suggests that the same protein-DNA recognition system used for transcription may also contribute to the earlier developmental events that bring about activation of the kappa locus.