| First Author | Madisen L | Year | 1994 |
| Journal | Genes Dev | Volume | 8 |
| Issue | 18 | Pages | 2212-26 |
| PubMed ID | 7958890 | Mgi Jnum | J:20523 |
| Mgi Id | MGI:68611 | Doi | 10.1101/gad.8.18.2212 |
| Citation | Madisen L, et al. (1994) Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells. Genes Dev 8(18):2212-26 |
| abstractText | In murine plasmacytoma and human Burkitt's lymphoma cells, one allele of c-myc is translocated into one of the immunoglobulin loci, resulting in a characteristic pattern of deregulated c-myc transcription. Translocation events between c-myc and the IgH locus segregate c-myc and the IgH intron enhancer to different reciprocal products in all plasmacytomas and in most Burkitt's lymphoma cells, suggesting that an additional element(s) capable of affecting c-myc expression over a large and variable distance must exist in the IgH locus. The region 3' of the IgH C alpha gene contains four tissue-specific and cell stage-specific DNase I hypersensitive sites (HSs), two of which map to the late B cell-specific 3' C alpha enhancer. We report here that DNA sequences comprising the two other 3' C alpha HSs contain potential protein-binding motifs for trans-activators commonly associated with immunoglobulin enhancers and that these sites can function as cell stage-specific enhancers in transient B cell assays. A DNA fragment containing all four HSs (HS1234) synergistically activates c-myc transcription in plasmacytoma and Burkitt's lymphoma cells in transient assays and induces high-level transcription, a promoter shift from P2 to P1, and an increase in readthrough transcription in stable transfections. Furthermore, plasmacytoma clones stably transfected with a HS1234-linked c-myc construct express c-myc in a position-independent, copy number-dependent manner. These results suggest that HS1234 may function as a locus control region (LCR), deregulating c-myc expression in t(15;12) plasmacytomas, as well as potentially contributing to aspects of normal IgH chain expression. |
