Regulation of Geminin and Cdt1 expression by E2F transcription factors

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Abstract
Geminin and Cdt1 play an essential role in the initiation of DNA replication, by regulating the chromatin loading of the MCM complex. In this study, we showed that the transcription of human Geminin and Cdt1, as well as that of MCM7, is activated by transcription factors E2F1–4, but not by factors E2F5–7. Analysis of various Geminin and Cdt1 promoter constructs showed that an E2F-responsive sequence in the vicinity of the transcription initiation site is necessary for the transcriptional activation. The promoter activity for human Geminin was activated by the E7, but not E6, oncogene of human papillomavirus type 16. While E2F1-induced activation of human Cdt1 gene transcription was suppressed by pRb, but not by p107 or p130, its E2F4-induced activation was suppressed by pRb, p107, and p130. Furthermore, the promoter activities of human Geminin and Cdt1 were demonstrated to be growth-dependent. Taken together, the results demonstrate that Geminin and Cdt1 constitute targets for various members of the E2F family of transcription factors, and that expression of Geminin and Cdt1 is perhaps mediated by the activation of a pRb/E2F pathway.