DNA topoisomerase II cleaves at specific sites in the 5' flanking region of c-fos proto-oncogenes in vitro.
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.
D001483:Base Sequence; D002467:Cell Nucleus / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D010957:Plasmids; D011519:Proto-Oncogenes; D013379:Substrate Specificity
D004247:DNA; D004250:DNA Topoisomerases, Type II