The intron enhancer of the immunoglobulin kappa gene activates c-myc but does not induce the Burkitt-specific promoter shift.
In Burkitt's lymphoma cells the c-myc gene locus is consistently fused to the constant region of one of the immunoglobulin genes by chromosomal translocation. The translocated c-myc gene is transcriptionally activated and preferentially transcribed from the P1 promoter whenever the exon-intron structure of c-myc remains intact. In order to define elements involved in this promoter shift we have cloned the translocated c-myc allele from Burkitt's lymphoma cell line BL60, which is characterized by several point mutations. The mutated c-myc allele of BL60 was stably introduced into baby hamster kidney and Burkitt's lymphoma cells. S1 nuclease and RNAase protection mapping experiments demonstrated that the mutated c-myc allele was expressed at a low level and with a normal promoter usage (P2 greater than P1) in Burkitt's lymphoma and baby hamster kidney cells. Furthermore, we have studied the expression of a construct consisting of the mutated c-myc allele, part of the bvr1 (Burkitt's variant rearranging region 1) locus, the human immunoglobulin kappa constant region, and the kappa intron enhancer after stable transfection into Burkitt's lymphoma cells. Although c-myc expression was about fivefold increased, the transcripts still initiated predominantly at promoter P2. This indicates that 5 kb of the constant kappa light-chain locus including the kappa intron enhancer is not sufficient to induce the Burkitt's lymphoma-specific promoter shift.
Polack
A
A
Institut für Klinische Molekularbiologie und Tumorgenetik, GSF, München, Germany.
Strobl
L
L
Feederle
R
R
Schweizer
M
M
Koch
E
E
Eick
D
D
Wiegand
H
H
Bornkamm
G W
GW
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000502:physiology*; D007438:Introns / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
D007145:Immunoglobulin kappa-Chains