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Vol. 15, No. 16, pp. 2146-2160, August 15, 2001
1 Massachusetts General Hospital Cancer Center,
Charlestown, Massachusetts 02129, USA; 2 Cancer Research
Campaign, Department of Oncology, University of Cambridge
CB2 2XY, UK; 3 Department of Genetics, University of
Cambridge CB2 3EH, UK
E2F is a heterogenous transcription factor and its role in cell
cycle control results from the integrated activities of many different
E2F family members. 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-regulated genes in vivo. dE2F1 is a potent activator of
transcription, and the loss of de2f1 results in the reduced
expression of E2F-regulated genes. In contrast, dE2F2 represses the
transcription of E2F reporters and the loss of de2f2 function
results in increased and expanded patterns of gene expression. The loss
of de2f1 function has previously been reported to compromise
cell proliferation. de2f1 mutant embryos have reduced
expression of E2F-regulated genes, low levels of DNA synthesis, and
hatch to give slow-growing larvae. We find that these defects are due
in large part to the unchecked activity of dE2F2, since they can be
suppressed by mutation of de2f2. Examination of eye discs from
de2f1; de2f2 double-mutant animals reveals that relatively 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 pattern transcription and how the net effect of E2F on cell
proliferation results from the interplay between two types of E2F
complexes that have antagonistic functions.
[Key Words: E2F; cell cycle; Drosophila]
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