Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma

In Burkitt's lymphoma (BL) cells the proto-oncogene c-myc is juxtaposed to one of the immunoglobulin (Ig) loci on chromosomes 2, 14, or 22, The c-myc gene becomes transcriptionally activated as a consequence of the chromosoma l translocation and shows preferential usage of promoter P1 over P2, a phen omenon referred to as promoter shift. In order to define the responsible re gulatory elements within the Ig lambda locus, we studied the effect of the human Ig lambda enhancer (HuE lambda) on c-myc expression after stable tran sfection into BL cells. A 12 kb genomic fragment encompassing HuE lambda, b ut not HuE lambda alone, strongly activated c-myc expression and induced th e promoter shift. To identify additional elements involved in c-myc deregul ation, we mapped DNaseI hypersensitive sites within the 12 kb lambda fragme nt on the construct. Besides one hypersensitive site corresponding to HuE l ambda, three additional sites were detected, Two of these elements displaye d enhancer activity after transient transfection. The third element did not activate c-myc transcription, but was required for full c-myc activation a nd promoter shift. Deletion analyses of the c-myc promoter identified the i mmediate promoter region as sufficient for activation by the Ig lambda locu s, but also revealed that induction of the promoter shift requires addition al upstream elements.