Cell cycle regulation ofcdc25Ctranscription is mediated by the periodic repression of the glutamine-rich activators NF-Y and Sp1

Abstract

The late S/G₂-specific transcription of the human cdc25C gene is dependent on an initiator-proximal repressor element (CDE) and an upstream activating sequence (UAS) of undefined nature. We now show that these upstream sequences harbour multiple in vivo protein binding sites that interact with transcrilptional activators and form separable, context-independent functional modules. Major components of the UAS are a bona fide Sp1 site and three direct sequence repeats (Y_c The Y_c-boxes interact with the CCAAT-box binding protein NF-Y and are criticaily dependent on synergistic interactions for efficient transcription activation. The NF-Y complexes, as well as Sp1, are constitutive activators, whose activation function is periodically repressed through the CDE. These observations indicate that the cell cycle regula tion of cdc25C transcription is mainly due to the CDE-medlated repression of glutamine-rich activators.