Activity of the human cytochrome c(1) promoter is modulated by E2F

The human cytochrome c(1) promoter is strongly activated in transfected Dro sophila SL2 cells expressing exogenous human E2F1. Transfection-deletion ex periments, DNase I protection by E2F1 and gel mobility-shift experiments lo cate E2F1 activation sites to two regions on either side of the transcripti on start site. Deletion of either region prevents E2F1 activation in transf ected SL2 cells, suggesting a co-operative interaction between them. E2F6, a member of the E2F family that lacks transactivation domains but contains specific suppressor domains, inhibits cytochrome c(1) promoter activity whe n co-transfected into HeLa cells, indicating that the E2F proteins modulate the cytochrome c(1) promoter in mammalian cells. However, E2F is not a gen eral regulator of oxidative phosphorylation genes since three additional nu clear-encoded mitochondrial genes were unaffected by E2F1 or E2F6.