A CORRELATION BETWEEN DEXAMETHASONE INDUCIBILITY AND BASAL EXPRESSIONLEVELS OF RETROVIRAL VECTOR PROVIRUSES

Identical transcription units inserted at different positions of mamma lian chromosomes may vary widely in transcriptional activity. We have used a set of ten cell clones with random unselected single integratio ns of retroviral vectors to study such position effects. The vector us ed carries a neo gene driven by the Akv murine leukemia virus long ter minal repeat that has only a weak promoter- enhancer activity in the t arget cell, the lymphoid cell line L691. Under transient expression co nditions, the strength of the Akv promoter - enhancer in the L691 cell s is increased by dexamethasone. In cell clones with single vector int egrations, a correlation is observed between the non-induced expressio n levels and the degree of dexamethasone induction. The strongest rela tive induction is found for the integrated vectors with the lowest non -induced expression levels and approaches the inducibility under trans ient expression. These results indicate that expression levels are com posed of distinct contributions from the integrated vector and from th e site of integration and are best explained in terms of a model in wh ich the sites of chromosomal integration exert variable positive enhan cer effects upon vector transcription.