IMMUNOGLOBULIN GENE-TRANSCRIPTION CEASES UPON DELETION OF A DISTANT ENHANCER

The tissue-specific E mu enhancer within the immunoglobulin heavy chai n (IgH) locus has recently been shown to be essential for efficient V region gene assembly in early B lineage cells. However, we and others have shown that late stage, Ig-secreting cells can produce IgH in the absence of E mu. In the present study we have explored the notion that another enhancer found in the far 3' region of the IgH locus (3'alpha E) takes on an important regulatory role in cells that have reached t his terminal stage in B cell development, The technique of homologous recombination was used to disrupt the 3'alpha E region in an E mu-defi cient, Ig gamma 2a-secreting cell line. Loss of 3'alpha E completely a bolished Ig heavy chain gene expression, demonstrating that transcript ion of this gene was dependent upon sequences that reside over 70 kb d ownstream. The ability of these sequences to function efficiently in t he absence of E mu may also provide an explanation for deregulated c-m yc expression in many Ig-secreting tumors.