Identification of Transcriptional Factor(s) which regulates Ig gene expression

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Immunoglobulin heavy-chain (IgH) gene expression is regulated in a large part by the IgH gene intronic enhancer which is composed of certain protein-binding motifs. These motifs act as a DNA element which is important for the regulation of the IgH gene trasncription. Two of these motifs, HE2 and E6 in the human IgH gene intronic enhancer, are considered to affect the B cell-specific gene expression. E6 was found to function as a silencer in non-lymphoid cells. It is very important to identify the regulatory molecules acting on these elements and their in vivo function. To examine the true function of the HE2 and E6 motifs in vivo, we established transgenic mouse lines. A 3^'deletion mutant of the IgH gene intronic enhancer which includes an active HE2 motif showed almost the same degree of trnascriptional activity and tissue-specificity as the whole IgH gene intronic enhancer. Still more, using the luciferase-assay, it was confirmed at cellular level that the HE2 motif plays an important role in the tissue-specific activity of the IgH gene intronic enhancer. On the other hand, the E6 motif was in some non-B cells.In transgenic mice, the IgH gene intronic enhancer functioned not only in B-lymphocytes but also in choroid plexus cells which are similar to glial cells. This suggests the existence of common gene expression control mechanisms between the immune system and the nervous system.