Stimulation of SV40 DNA replication by the human c‐myc enhancer

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Abstract
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) orl/promoter as a model system. The SV40 enhancer is known to enhance transcription from its orlpromoter, 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 Cost 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.