Functional antagonism between E2F family members

E2F is a heterogenous transcription factor and its role in cell cycle contr ol results from the integrated activities of many different E2F family memb ers. Unlike mammalian cells, that have a large number of E2F-related genes, the Drosophila genome encodes just two E2F genes, de2f1 and de2f2. Here we show that de2f1 and de2f2 provide different elements of E2F regulation and that they have opposing functions during Drosophila development. dE2F1 and dE2F2 both heterodimerize with dDP and bind to the promoters of E2F-regula ted genes in vivo. dE2F1 is a potent activator of transcription, and the lo ss of de2f1 results in the reduced expression of E2F-regulated genes. In co ntrast, dE2F2 represses the transcription of E2F reporters and the loss of de2f2 function results in increased and expanded patterns of gene expressio n. The loss of de2f1 function has previously been reported to compromise ce ll proliferation. de2f1 mutant embryos have reduced expression of E2F-regul ated genes, low levels of DNA synthesis, and hatch to give slow-growing lar vae. We find that these defects are due in large part to the unchecked acti vity of dE2F2, since they can be suppressed by mutation of de2f2. Examinati on of eye discs from de2f1; de2f2 double-mutant animals reveals that relati vely normal patterns of DNA synthesis can occur in the absence of both E2F proteins. This study shows how repressor and activator E2Fs are used to pat tern transcription and how the net effect of E2F on cell proliferation resu lts from the interplay between two types of E2F complexes that have antagon istic functions.