Murine and human 3' IgH regulatory sequences

Abstract

Both murine plasmacytomas and human Burkitt lymphomas contain chromosomal translocations involving the c-myc gene and the Ig gene cluster. As a result of the translocation in mouse plasmacytomas, the myc oncogene comes under the influence of regulatory sequences 3 of the murine IgH gene cluster. The murine 3 regulatory region contains four enhancers, three of which are located in a 25 kb unit of dyad symmetry [8, 14]. This unit contains a central enhancer, flanked by two identical enhancers at the termini, and we have speculated that this unit has entered the mouse genome during evolution as a transposable element. The fourth, and most downstream, enhancer comprises a separate structural and functional unit. Synergy among these enhancers has been documented and it has been suggested that these elements comprise a locus control region [6]. We have identified two virtually identical human enhancers 3 of the IgH locus, one downstream of the Cα1 gene and one downstream of the Cα2 gene. These bear a region of homology to one of the mouse 3 enhancers, and are predicted to play a role in myc ontogenesis. Preliminary evidence for DNA rearrangements of 3 regulatory sequences in human myeloma cell lines is presented.