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Polack, A. ; Feederle, R. ; Klobeck, G. ; Hörtnagel, K.

Regulatory elements in the immunoglobulin kappa locus induce c-myc activation and the promoter shift in Burkitt's lymphoma cells.

EMBO J. 12, 3913-3920 (1993)
PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
In Burkitt's lymphoma cells the proto-oncogene c-myc is constantly juxtaposed through chromosomal translocation to one of the immunoglobulin loci on chromosomes 14, 2 or 22. In the majority of cases the chromosomal breakpoint is localized 3' or 5' of the gene leaving the physiological c-myc transcription unit intact. As a consequence of the translocation the c-myc gene on the translocation chromosome becomes transcriptionally activated in such a manner that the c-myc promoter P1 is more active than promoter P2. In order to define elements involved in c-myc activation through t(2;8) translocation we have studied the expression of constructs consisting of c-myc and different parts of the immunoglobulin kappa locus after stable transfection into Burkitt's lymphoma cells. The c-myc gene under the control of the complete Ig kappa locus containing matrix attachment region, intron enhancer, constant kappa gene and 3' enhancer was strongly activated with predominant usage of promoter P1. Deletion analysis revealed that the intron or 3' enhancers alone activated c-myc to a much lesser extent and with normal promoter usage (P1 < P2). The cooperation of the same regulatory elements is required not only for transcriptional activation and induction of the promoter shift but also for down-regulation of promoter P1 of the translocated c-myc allele by sodium butyrate, another characteristic feature of Burkitt's lymphoma cells. This supports the notion that all elements involved in transcriptional activation and dysregulation of c-myc are contained within the myc-Ig specific minichromosome.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Burkitt's Lymphoma ; C-myc ; Oncogene Deregulation ; Promoter Shift ; Sodium Butyrate
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Quellenangaben Band: 12, Heft: 10, Seiten: 3913-3920 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Heidelberg, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)