摘要：SummaryCyclin E is a key factor for S phase entry, and deregulation of Cyclin E results in developmental defects and tumors. Therefore, proper cycling of Cyclin E is crucial for normal growth. Here we found that transcription factors Apontic (Apt) and E2f1 cooperate to inducecyclin EinDrosophila. Functional binding motifs of Apt and E2f1 are clustered in the first intron ofDrosophila cyclin Eand directly contribute to thecyclin Etranscription. Knockout ofaptande2f1together abolished Cyclin E expression. Furthermore, Apt up-regulates Retinoblastoma family protein 1 (Rbf1) for proper chromatin compaction, which is known to represscyclin E. Notably, Apt-dependent up-regulation of Cyclin E and Rbf1 is evolutionarily conserved in mammalian cells. Our findings reveal a unique mechanism underlying the induction and subsequent decline of Cyclin E expression.Graphical AbstractDisplay OmittedHighlights•Mutual activation ofaptande2f1promotes rapid induction of CycE at S phase entry•Apt also up-regulates Rbf1, but Rbf1 is inactivated through phosphorylation by Cdk2•After initiation of S phase, Rbf1 becomes active and repressescycE•Apt governs both induction and subsequent repression ofcycEBiological Sciences; Molecular Biology; Cell Biology
