A NOVEL UPSTREAM ELEMENT COMPENSATES FOR AN INEFFECTUAL OCTAMER MOTIF IN AN IMMUNOGLOBULIN V-KAPPA PROMOTER

The octamer (or dc/cd) motif is considered to be a critical component of all immunoglobulin (Ig) promoters. Although the sequence of this motif is highly conserved among most Ig promoters, there are some notable examples in which efficiently expressed Ig genes contain divergent octamers with base substitutions that are demonstrably deleterious when tested with heterologous proximal promoter elements. To elucidate the mechanisms that enable these naturally occurring Ig genes to cope with divergent octamers, we analyzed two such promoters with regard to their ability to interact with relevant transcription factors. We found that the divergent octamer in the χ0 germline promoter strongly binds both Oct-1 and Oct-2 factors, presumably because of compensatory contributions by flanking DNA sequences. A more surprising result was obtained with the V(χ)19 promoter. In this case, the divergent octamer is a very weak Oct factor binding site and, without help from another upstream element, is inadequate for efficient promotor function. This additional element, termed χY because of its high pyrimidine content (CTTCCTTA), serves as a binding site for a novel lymphoid-specific factor. When the divergent V(χ)19 octamer was converted to a strong Oct factor binding site by a single point mutation, the need for κY was obviated. Interestingly, V(H) promoters that contain the same divergent octamer also contain an upstream element that is very similar to κY.