Synergies between regulatory elements of the immunoglobulin heavy chain locus and its palindromic 3' locus control region.

Transcriptional enhancers of the IgH locus include E mu and four 3' elements (C alpha3', hs1-2, hs3 and hs4), some of which are by themselves weak. We show that these weak elements behave as strong "co-enhancers" when combined, and display a stage-dependent activity which differs from that obtained when they are alone. Combinations mimicking the palindromic structure of the 3' IgH region are particularly efficient. Noticeably in pre-B cells, hs4 is boosted by the addition of elements previously considered inactive at this stage, hs1-2 and hs3. Combinations of 3' elements also strongly boost E mu at all maturation stages, but inhibitory interactions occasionally occur between E mu and incomplete 3' combinations, indicating that full transcriptional activity is mainly achieved when all 5' and 3' partners play their respective roles.