DEVELOPMENTAL CONTROL OF THE G(1) TO S-TRANSITION IN DROSOPHILA - CYCLIN-E IS A LIMITING DOWNSTREAM TARGET OF E2F

The E2F transcription factor is required for S phase in Drosophila. Wh ile it also triggers expression of replication genes at the G1-S trans ition, the relevance of this transcription is not clear because many o f the induced gene products are sufficiently stable that new expressio n is not required for S phase. However, one unstable product could cou ple S phase to E2F activation. Here we show that cyclin E expression a t G1-S requires E2F, that activation of E2F without cyclin E is not su fficient for S phase, and that early in G(1) ectopic expression of cyc lin E alone can bypass E2F and induce S phase. We conclude that cyclin E is the downstream gene that couples E2F activity to G(1) control. N ot all embryonic cycles are similarly coupled to E2F activation, howev er. The rapidly proliferating CNS cells, which exhibit no obvious G(1) , express cyclin E constitutively and independently of E2F. Instead, c yclin E expression activates E2F in the CNS. Thus, this tissue-specifi c E2F-independent transcription of cyclin E reverses the hierarchical relationship between cyclin E and E2F. Both hierarchies activate expre ssion of the full complement of replication functions controlled by E2 F; however, whereas inactivation of E2F can produce a G(1) when cyclin E is downstream of E2F, we propose that an E2F-independent source of cyclin E eliminates G(1).