M. Duch et al., A CORRELATION BETWEEN DEXAMETHASONE INDUCIBILITY AND BASAL EXPRESSIONLEVELS OF RETROVIRAL VECTOR PROVIRUSES, Nucleic acids research, 21(20), 1993, pp. 4777-4782
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.