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Identification of novel E2F1 target genes regulated in cell cycle-dependent and independent manners

Oncogene volume 25, pages 1786–1798 (2006)Cite this article

Abstract

The transcription factor E2F mediates cell cycle-dependent expression of genes important for cell proliferation in response to growth stimulation. To further understand the role of E2F, we utilized a sensitive subtraction method to explore new E2F1 targets, which are expressed at low levels and might have been unrecognized in previous studies. We identified 33 new E2F1-inducible genes, including checkpoint genes Claspin and Rad51ap1, and four genes with unknown function required for cell cycle progression. Moreover, we found three groups of E2F1-inducible genes that were not induced by growth stimulation. At least, two groups of genes were directly induced by E2F1, indicating that E2F1 can regulate expression of genes not induced during the cell cycle. One included Neogenin, WASF1 and SGEF genes, which may have a role in differentiation or development. The other was the cyclin-dependent kinase inhibitor p27Kip1, which was involved in suppression of inappropriate cell cycle progression induced by deregulated E2F. E2F1-responsive regions of these genes were located more upstream than those of typical E2F targets and did not have typical E2F sites. These results indicate that there are groups of E2F1 targets, which are regulated in a distinct manner from that of typical E2F targets.

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Acknowledgements

We thank K Helin for kindly providing U2OS-ER-E2F1 cells, K Maruyama for p27Kip1 reporters, M Ikeda for critically reading the manuscript, S Morinaga, E Ozono, Y Arioka, A Wakita, R Suzuki and M Murayama for technical assistance, as well as K Ogawa and K Nagata for help in setting up PCR/subtraction procedure. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from The Ministry of Education, Culture, Sports, Science and Technology, and in part by a grant from NOVARTIS Foundation (Japan) for the Promotion of Science.

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Authors and Affiliations

  1. Human Gene Sciences Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

    R Iwanaga, H Komori & K Ohtani

  2. Division of Pharmacology, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan

    S Ishida

  3. Laboratory of Microbiology and Immunology, Graduate School of Health Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

    R Iwanaga & N Okamura

  4. Department of Developmental Biology, Center for Translational and Advanced Animal Research on Human Disease, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan

    K Nakayama

  5. Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    K I Nakayama

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  1. R Iwanaga
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  2. H Komori
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Correspondence to K Ohtani.

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Iwanaga, R., Komori, H., Ishida, S. et al. Identification of novel E2F1 target genes regulated in cell cycle-dependent and independent manners. Oncogene 25, 1786–1798 (2006). https://doi.org/10.1038/sj.onc.1209210

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