Absence of a paused transcription complex from the c-myc P2 promoter of the translocation chromosome in Burkitt's lymphoma cells: implication for the c-myc P1/P2 promoter shift.
We have shown recently that pausing of RNA polymerase II (pol II) at the transcription start site regulates expression from the P2 promoter of the proto-oncogene c-myc. RNAs initiated at the P2 promoter usually contribute > 80% to steady-state c-myc RNA levels in normal cells. In Burkitt's lymphoma (BL) cells c-myc is chromosomally translocated to an immunoglobulin (Ig) gene and preferentially transcribed from the upstream P1 promoter. We have studied the activity of c-myc promoters in two BL cell lines with high expression of P1 RNA. Kinetic nuclear run-on experiments show that the initiation rate at the c-myc P1 promoter in BL2 and BL60 cells is not increased compared with control BJAB cells, whereas the number of paused polymerases at the P2 promoter is greatly diminished. The translocation c-myc gene of BL60 cells was cloned and stably transfected into the BL cell line Raji. The transfected c-myc gene regained the ability to form a paused transcription complex at the c-myc P2 promoter. The data suggest that a paused polymerase at the c-myc P2 promoter impedes transcription from the upstream P1 promoter on a normal c-myc gene. The c-myc gene on the translocation chromosome in BL cells has lost the ability to retain pol II at the P2 promoter, probably by interaction with elements of the adjacent Ig gene locus.
Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, Munich, Germany.
L J
LJ
Strobl
F
F
Kohlhuber
J
J
Mautner
A
A
Polack
D
D
Eick
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004742:Enhancer Elements, Genetic; D005091:Exons; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D012319:RNA Polymerase II / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007145:Immunoglobulin kappa-Chains; C000715470:MAS1 protein, human; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm; D012319:RNA Polymerase II