In addition to Eμ, several elements downstream of the IgH cluster, i.e. 3' of the Cα gene, areinvolved in regulating IgH gene rearrangement and expression. This entire downstream regulatory region was shown to be deleted in the mutant myeloma cell line, LP1.2. The deletion encompasses ∼34 kb and is presumably responsible for the reduced levels of IgH expression in this cell line. An additional regulatory element, included in the LP1.2 deletion, was identified by investigation of a DNase I hypersensitivity site located -.33 kb downstream of the α gene and present in pre-B and plasma cells. This novel IgH gene enhancer element, termed 3'α-hs4, is capable of activity through out B cell development. Transient transfectlon of 3'α-hs4 in a CAT reporter gene construct shows transcriptional enhancement activity approximating that of Eμ in S194 plasmacytoma and M12.4.1 and A-20 B cell lines; while in apre-B cell line, 18-81, the average activity is 25% that of Eμ. Enhancer activity was localized to an800 bp fragment. The activity of 3'α-hs4 is orientation independent and appears to be B cell specific. Tight regulation of 3'α-hs4 is inferred from its variable activity in different plasmacytoma cell lines and within the pie B cell line, 18-81.
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