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Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter

Oncogene volume 22, pages 7632–7641 (2003)Cite this article

Abstract

The activity of E2F transcription factors plays a crucial role in mammalian cell-cycle progression and is controlled by physical association with the pocket proteins (pRb and its related p107 and p130). The E2F1 promoter, which contains two overlapping E2F-binding sites, is activated at the G1/S transition in an E2F-dependent manner. Mutational experiments have shown that the distal E2F-binding site on the E2F1 promoter is required for transcriptional repression in the G0 phase, whereas the proximal E2F-binding site contributes to transcriptional activation at the G1/S boundary. Consistent with these results, chromatin immunoprecipitation assays have revealed that the E2F4/p130 repressor complex specifically binds to the distal E2F-binding site, whereas E2F1 and E2F3 activators preferentially bind to the proximal E2F-binding site. The assays also showed that the specific binding of E2F4/p130 complex to the distal site was dramatically impaired by a mutation introduced into the contiguous repression site (cell Cycle gene Homology Region; CHR). Taken together, these findings indicate that the two E2F-binding sites play distinct roles in the regulation of E2F1 transcription by interacting with different sets of E2F members and cooperating with the contiguous repressor element.

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Acknowledgements

This work was supported in part by the Grant-in-Aid for General Scientific Research and Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan and Japan Society for the Promotion of Science and in part by ‘Ground Research for Space Utilization’ promoted by NASDA and Japan Space Forum.

We thank Dr K Ohtani for pBS-GAPDH and for critically reading the manuscript, members of SME for support and useful discussions, and Solachuddin JA. Ichwan for excellent technical assistance.

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Authors and Affiliations

  1. Section of Molecular Craniofacial Embryology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Keigo Araki, Kazuhiro Eto & Masa-Aki Ikeda

  2. Section of Oral Surgery, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Yusuke Nakajima

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  1. Keigo Araki
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Correspondence to Masa-Aki Ikeda.

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Araki, K., Nakajima, Y., Eto, K. et al. Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter. Oncogene 22, 7632–7641 (2003). https://doi.org/10.1038/sj.onc.1206840

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