CYCLIN-DEPENDENT KINASE ACTIVATION AND S-PHASE INDUCTION OF THE CYCLIN B1 GENE ARE LINKED THROUGH THE CCAAT ELEMENTS

Control of cell proliferation is dependent on the regulated expression of the cyclin genes. Induction of cyclin BI gene expression in S phas e has been shown to require sequences within the first 90 bp of the pr oximal promoter region, In this study, we defined the cell cycle regul atory elements within this region and explored the mechanism by which the cyclin BI gene is activated, A CDE-like element that is important in S-phase regulation of other genes was not required for correct cell cycle expression of cyclin B1. Instead, two CCAAT boxes were essentia l for S-phase induction of cyclin B1 gene in both NIH3T3 and HeLa cell s, Induction of cyclin B1 by cyclin/cyclin-dependent kinase (cdk) comp lexes was examined by cotransfection of the reporter along with approp riate expression vectors, Complexes of cdk4 with cyclin D1 or cdk2 wit h cyclin E or A can activate the cyclin Bf promoter, and activation is uniquely dependent on the CCAAT elements in both normal and heterolog ous contexts. The transcription factor NF-Y binds to both CCAAT elemen ts, These findings suggest that S phase-specific induction of the cycl in B1 promoter is dependent upon NF-Y binding to the CCAAT elements an d is correlated with activation by cyclin-dependent kinases.