Rbf1-independent termination of E2f1-target gene expression during early Drosophila embryogenesis.
The initiation and maintenance of G1 cell cycle arrest is a key feature of animal development. In the Drosophila ectoderm, G1 arrest first appears during the seventeenth embryonic cell cycle. The initiation of G1(17) arrest requires the developmentally-induced expression of Dacapo, a p27-like Cyclin E-Cdk2 inhibitor. The maintenance of G1(17) arrest requires Rbf1-dependent repression of E2f1-regulated replication factor genes, which are expressed continuously during cycles 1-16 when S phase immediately follows mitosis. The mechanisms that trigger Rbf1 repressor function and mediate G1(17) maintenance are unknown. Here we show that the initial downregulation of expression of the E2f1-target gene RnrS, which occurs during cycles 15 and 16 prior to entry into G1(17), does not require Rbf1 or p27(Dap). This suggests a mechanism for Rbf1-independent control of E2f1 during early development. We show that E2f1 protein is destroyed in a cell cycle-dependent manner during S phase of cycles 15 and 16. E2f1 is destroyed during early S phase, and requires ongoing DNA replication. E2f1 protein reaccumulates in epidermal cells arrested in G1(17), and in these cells the induction of p27(Dap) activates Rbf1 to repress E2f1-target genes to maintain a stable G1 arrest.
Shibutani
Shusaku
S
Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Swanhart
Lisa M
LM
Duronio
Robert J
RJ
D000818:Animals; D002453:Cell Cycle; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D016193:G1 Phase; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016160:Retinoblastoma Protein; D016196:S Phase; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D019927:Cyclin E; D029721:Drosophila Proteins; D050687:E2F1 Transcription Factor; D009687:Nuclear Proteins; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C103336:dap protein, Drosophila; D051357:Cyclin-Dependent Kinase 2; C495887:cdk2 protein, Drosophila