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We have investigated the role of sequence motifs in the immunoglobulin heavy chain (IgH) enhancer on its activity in myeloma and fibroblast cell-lines. In transient transfection assays the transcription stimulatory activity of the enhancer is decreased in myeloma cells by mutating the E motifs 1, 2 and 3, the core motifs C1, C2, C3 and the octamer motif (OC) and in fibroblasts by mutating E2, E3, and C2. Our results suggest that transcription factors binding to E1, C1, C3 and OC contribute in a positive manner to the tissue specificity of the IgH enhancer.

Mutational analysis of the contribution of sequence motifs within the IgH enhancer to tissue specific transcriptional activation