CELL-CYCLE REGULATION OF CDC25C TRANSCRIPTION IS MEDIATED BY THE PERIODIC REPRESSION OF THE GLUTAMINE-RICH ACTIVATORS NF-Y AND SP1

The late S/G(2)-specific transcription of the human cdc25C gene is dep endent on an initiator-proximal repressor element (CDE) and an upstrea m activating sequence (UAS) of undefined nature. We now show that thes e upstream sequences harbour multiple in vivo protein binding sites th at interact with transcriptional activators and form separable, contex t-independent functional modules. Major components of the UAS are a bo na fide Sp1 site and three direct sequence repeats (Y-c-boxes). The Y- c-boxes interact with the CCAAT-box binding protein NF-Y and are criti cally dependent on synergistic interactions for efficient transcriptio n activation. The NF-Y complexes, as well as Sp1, are constitutive act ivators, whose activation function is periodically repressed through t he CDE. These observations indicate that the cell cycle regulation of cdc25C transcription is mainly due to the CDE-mediated repression of g lutamine-rich activators.