Stimulation of SV40 DNA replication by the human c-myc enhancer.
In earlier studies we had shown that a transcriptional enhancer sequence exists about 2 kb upstream of the human c-myc gene. The core sequence necessary for enhancer activity was defined therein as a 21 bp nucleotide element, which also showed autonomous replicating activity [EMBO J. (1988) 7, 3135-3142; EMBO J. (1989) 8, 4273-4279]. Recently, several reports have substantiated the notion that transcription and replication can be concertedly regulated in a larger number of cases than expected. In this report, we took the simian virus 40 (SV 40) ori/promoter as a model system. The SV40 enhancer is known to enhance transcription from its ori/promoter, but to reduce its replication (probably due to a negative feedback). The SV40 enhancer was replaced by the c-myc enhancer core in order to see its effect upon SV40 DNA replication and transcription. The results showed that besides stimulating transcription, the c-myc enhancer promoted SV40 DNA replication in monkey CosI cells. Stimulation was only observed when the c-myc enhancer was inserted in the 'up-to-down' orientation to the SV40 promoter. The promoting function of the c-myc enhancer on DNA replication correlated with the transcriptional activation function, as determined by systematic point mutations introduced within the 21 bp core sequence.
Kumano
M
M
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Nakagawa
T
T
Imamura
Y
Y
Galli
I
I
Ariga
H
H
Iguchi-Ariga
S M
SM
D000818:Animals; D001483:Base Sequence; D004261:DNA Replication / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D014779:Virus Replication
D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins