DNA topoisomerase II cleaves at specific sites in the 5′ flanking region of c-fos proto-oncogenes in vitro.

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Abstract
We have analyzed 1 kb of cloned human c‐fos sequence (‐711 to +287) for calf thymus DNA topoisomerase II cleavage sites in vitro. Using the anti‐tumor drug VP16 (demethylepipodophyllotoxin‐beta‐D‐glucoside) with purified topoisomerase II, we identify twelve sites. Five sites are clustered around position ‐306 in a region that possesses enhancer‐like properties. A second cluster of three sites is positioned 15 bp upstream of the TATA promoter element. With a HeLa nuclear extract as a source of topoisomerase II, a subset of cleavage sites is conserved within the two clusters. The cleavage sites in the enhancer‐like element are conserved in the homologous region of the murine c‐fos. These findings raise the possibility that topoisomerase II is involved in mediation of mitogen‐induced c‐fos expression.