Abstract
Cell cycle regulation of the cyclin A gene is determined by a bipartite repressor binding site in the region of the basal promoter, termed CDE-CHR, which also controls the expression of cell cycle genes upregulated in S or G2 (such as cdc25C). The CDE–CHR in the cyclin A promoter is recognized by both E2F complexes and CDF-1, but the contribution of each of these factors in cell cycle regulation is unknown. In the present study, we have introduced mutations into the cyclin A promoter which lead to either a loss or enhancement of E2F binding, while having only marginal effects on the interaction with CDF-1. Unlike mutants deficient for CDF-1 binding, promoter variants lacking E2F binding showed an unchanged repression in G0, thus identifying CDF-1 as the principal repressor of the cyclin A gene. The same mutants did show, however, a delayed derepression while a mutation leading to increased E2F binding resulted in premature up-regulation. These findings clearly suggest that E2F contributes to the correct timing of cyclin A transcription, presumably by acting as an anti-repressor. In agreement with this conclusion, we find that the cyclin A promoter only poorly interacts with E2F-4, which is the major E2F family member in G0 cells, while a clear binding is seen with E2F-1 and -3, which are up-regulated in late G1.
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Liu, N., Lucibello, F., Engeland, K. et al. A new model of cell cycle-regulated transcription: repression of the cyclin A promoter by CDF-1 and anti-repression by E2F. Oncogene 16, 2957–2963 (1998). https://doi.org/10.1038/sj.onc.1201838
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DOI: https://doi.org/10.1038/sj.onc.1201838
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