The Cell-Cycle Transcriptional Network Generates and Transmits a Pulse of Transcription Once Each Cell Cycle

Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components function together in the gene regulatory network remain unclear. Here we show that the TF network can generate and transmit a \"pulse\" of transcription independently of CDK oscillations. The premature firing of the transcriptional pulse is prevented by early G1 inhibitors, including transcriptional corepressors and the E3 ubiquitin ligase complex APCCdh1. We demonstrate that G1 cyclin-CDKs facilitate the activation and accumulation of TF proteins in S/G2/M phases through inhibiting G1 transcriptional corepressors (Whi5 and Stb1) and APCCdh1, thereby promoting the initiation and propagation of the pulse by the TF network. These findings suggest a unique oscillatory mechanism in which global phase-specific transcription emerges from a pulse-generating network that fires once-and-only-once at the start of the cycle.