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Regulation of Geminin and Cdt1 expression by E2F transcription factors

Oncogene volume 23, pages 3802–3812 (2004)Cite this article

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.

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Abbreviations

DHFR:

dihydrofolate reductase

pRb:

retinoblastoma protein

MCM:

minichromosome maintenance

HPV:

human papillomavirus

FBS:

fetal bovine serum

ChIP:

chromatin immunoprecipitation

HDAC:

histone deacetylase

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Acknowledgements

We thank Dr Joseph R Nevins (Duke University Medical Center), Dr Junji Magae (Institute of Research and Innovation, Japan), Dr Gustavo Leone (The Ohio State University), Dr Denise A Galloway (Fred Hutchinson Cancer Research Center), and Dr Robert A Weinberg (Whitehead Institute for Biomedical research, MIT) for providing expression plasmids. We also thank Yoshiko Sakamoto for her excellent assistance. This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work has been supported by CREST of JST (Japan Science and Technology Agency).

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  1. Genetic Diagnosis, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Kenichi Yoshida & Ituro Inoue

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  1. Kenichi Yoshida
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Correspondence to Kenichi Yoshida.

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Yoshida, K., Inoue, I. Regulation of Geminin and Cdt1 expression by E2F transcription factors. Oncogene 23, 3802–3812 (2004). https://doi.org/10.1038/sj.onc.1207488

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