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Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F

Oncogene volume 18, pages 2299–2309 (1999)Cite this article

Abstract

Initiation of DNA replication requires the function of MCM gene products, which participate in ensuring that DNA replication occurs only once in the cell cycle. Expression of all mammalian genes of the MCM family is induced by growth stimulation, unlike yeast, and the mRNA levels peak at G1/S boundary. In this study, we examined the transcriptional activities of isolated human MCM gene promoters. Human MCM5 and MCM6 promoters with mutation in the E2F sites failed in promoter regulation following serum stimulation and exogenous E2F expression. In addition, we identified a novel E2F-like sequence in human MCM6 promoter which cooperates with the authentic E2F sites in E2F-dependent regulation. Forced expression of E2F1 could induce expression of all members of the endogenous MCM genes in rat embryonal fibroblast REF52 cells. Our results demonstrated that the growth-regulated expression of mammalian MCM5 and MCM6 genes, and presumably other MCM members, is primarily regulated by E2F through binding to multiple E2F sites in the promoters.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for General Scientific Research and Cancer Research from the Ministry of Education, Science, Sports and Culture of Japan, in part by a grant for CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST) and in part by a grant from the Kanehara Foundation. We thank Y Matsumura and M Horimoto for their excellent technical assistance.

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Authors and Affiliations

  1. Human Gene Sciences Center, Tokyo Medical and Dental University, 113-8510, Tokyo, Japan

    Kiyoshi Ohtani, Ritsuko Iwanaga & Masataka Nakamura

  2. Department of Developmental Biology, Graduate School of Dentistry, Tokyo Medical and Dental University, 113-8549, Tokyo, Japan

    Masa-aki Ikeda

  3. Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 565-0871, Suita, Japan

    Norikazu Yabuta, Hiromichi Tsuruga & Hiroshi Nojima

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  1. Kiyoshi Ohtani
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Ohtani, K., Iwanaga, R., Nakamura, M. et al. Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F. Oncogene 18, 2299–2309 (1999). https://doi.org/10.1038/sj.onc.1202544

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