Transcription factor AP-4 is a ligand for immunoglobulin-kappa promoter E-box elements

Immunoglobulin (Ig)-kappa promoters from humans and mice share conserved se quences. The octamer element is common to all Ig promoters and pivotal for their function. However, other conserved sequence motifs, that differ betwe en Ig variable gene families, are required for normal promoter function. Th ese conserved motifs do not stimulate transcription in the absence of an oc tamer. One example is an E-box of the E47/E12 type (5-'CAGCTG-3'), which is found in all promoters of the human and murine Ig-kappa gene subgroups/fam ilies, with the exception of subgroups II and VI and their related murine f amilies. In the present study we show that the ubiquitously expressed trans cription factor AP-4, and not E47, interacts specifically with the kappa pr omoter E-boxes when tested in electrophoretic mobility-shift assays using n uclear extracts derived from human and murine B-cell lines. Furthermore, AP -4, unlike E47, did not act as a transactivator, which is in agreement with previous studies on intact kappa promoters, showing that transcription is absent when the octamer element has been mutated. Based on these data, and the conservation of the 5'-CAGCTG-3' motif among human and murine kappa pro moters, we propose that AP-4 is the major ligand for Ig-kappa promoter E-bo xes.