Developmental control of the G1 to S transition in Drosophila: cyclin Eis a limiting downstream target of E2F.
The E2F transcription factor is required for S phase in Drosophila. While it also triggers expression of replication genes at the G1-S transition, the relevance of this transcription is not clear because many of the induced gene products are sufficiently stable that new expression is not required for S phase. However, one unstable product could couple S phase to E2F activation. Here we show that cyclin E expression at G1-S requires E2F, that activation of E2F without cyclin E is not sufficient for S phase, and that early in G1 ectopic expression of cyclin E alone can bypass E2F and induce S phase. We conclude that cyclin E is the downstream gene that couples E2F activity to G1 control. Not all embryonic cycles are similarly coupled to E2F activation, however. The rapidly proliferating CNS cells, which exhibit no obvious G1, express cyclin E constitutively and independently to E2F. Instead, cyclin E expression activates E2F in the CNS. Thus, this tissue-specific E2F-independent transcription of cyclin E reverses the hierarchical relationship between cyclin E and E2F. Both hierarchies activate expression of the full complement of replication functions controlled by E2F; however, whereas inactivation of E2F can produce a G1 when cyclin E is downstream of E2F, we propose that an E2F-independent source of E eliminates G1.
Duronio
R J
RJ
Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.
O'Farrell
P H
PH
D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D050684:E2F Transcription Factors; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005246:Feedback; D016193:G1 Phase / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D018840:HSP70 Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors