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Nucleic Acids Research, 1993, Vol. 21, No. 20 4777-4782
© 1993

MOLECULAR BIOLOGY

A correlation between dexamethasone inducibility and basal expression levels of retroviral vector proviruses

Mogens Duch, Kirsten Paludan, Jette Lovmand, Lene Pedersen, Poul Jørgensen and Finn Skou Pedersen*

Department of Molecular Biology, University of Aarhus C.F.Mølle Allé, Bldg. 130, DK-8000 Arhus C, Denmark

*To whom correspondence should be addressed.

Received July 1, 1993. Revised September 1, 1993. Accepted September 1, 1993.

Identical transcription units inserted at different positions of mammalian chromosomes may vary widely in transcriptional activity. We have used a set of ten cell clones with random unselected single integrations of retroviral vectors to study such position effects. The vector used carries a neo gene driven by the Akv murine leukemia virus long terminal repeat that has only a weak promoter- enhancer activity in the target cell, the lymphoid cell line L691. Under transient expression conditions, the strength of the Akv promoter - enhancer in the L691 cells is increased by dexamethasone. In cell clones with single vector integrations, a correlation is observed between the noninduced expression levels and the degree of dexamethasone induction. The strongest relative induction is found for the integrated vectors with the lowest non-induced expression levels and approaches the inducibility under transient expression. These results indicate that expression levels are composed of distinct contributions from the integrated vector and from the site of integration and are best explained in terms of a model in which the sites of chromosomal integration exert variable positive enhancer effects upon vector transcription.


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