DNA-BINDING AND TRANSACTIVATION PROPERTIES OF DROSOPHILA E2F AND DP PROTEINS

The temporal activation of E2F transcriptional activity appears to be an important component of the mechanisms that prepare mammalian cells for DNA replication. Regulation of E2F activity appears to be a highly complex process, and the dissection of the E2F pathway will be greatl y facilitated by the ability to use genetic approaches. We report the isolation of two Drosophila genes that can stimulate E2F-dependent tra nscription in Drosophila cells. One of these genes, dE2F, contains thr ee domains that are highly conserved in the human homologs E2F-1, E2F- 2, and E2F-3. Interestingly, one of these domains is highly homologous to the retinoblastoma protein (RB)-binding sequences of human E2F gen es, The other gene, dDP, is closely related to the human DP-1 and DP-2 genes. We demonstrate that dDP and dE2F interact and cooperate to giv e sequence-specific DNA binding and optimal trans-activation. These fe atures suggest that endogenous Drosophila E2F, like human E2F, may be composed of het erodimers and may be regulated by RB-Like proteins. Th e isolation of these genes will provide important reagents for the gen etic analysis of the E2F pathway.