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  • Original Paper
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In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated transcriptional repression

Oncogene volume 20, pages 6039–6047 (2001)Cite this article

Abstract

We previously reported that overexpression of PU.1, a member of the Ets family of transcription factors, induces differentiation inhibition and apoptosis associated with c-Myc down-regulation in murine erythroleukemia (MEL) cells. To understand the molecular mechanism by which c-Myc is down-regulated due to overexpression of PU.1, we performed luciferase reporter assays using the mouse c-myc promoter. PU.1 repressed the activities of not only the c-myc promoter but also several other promoters. Experiments with deletion mutants of PU.1 revealed that the C-terminal region spanning amino acids (aa) 123–272 including the PEST and ETS domains but not the activation ___domain was sufficient for this transcriptional repression. It was unlikely that the repression was due to sequestration of a limited amount of CBP/p300 nor pCAF, because overexpression of these co-activators did not relieve PU.1-mediated transcriptional repression. Instead, it was found that the C-terminal aa 101–272 of PU.1 formed a complex with mSin3A and HDAC1 in vivo, which was speculated to be associated with the repression. The C-terminal region of PU.1 also formed a complex with the basic transcription factor TBP in vitro and in vivo. Our results suggest that overexpression of PU.1 induces transcriptional repression in several gene promoters including the c-myc promoter which may be mediated by its complex formation with HDACs.

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Acknowledgements

We wish to thank Dr I Kitabayashi for the plasmid of HDAC1 and mSin3A. We also thank Drs M Yoneyama and Y Negishi for their helpful suggestions and advice. This work was supported by Grants-in-Aid for Specific Project Research from the Ministry of Education, Science and Culture, Japan. We are also grateful for financial support from the Uehara Memorial Foundation, Tokyo, Japan, and from the Akiyama Memorial Hospital, Hakodate, Japan.

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Authors and Affiliations

  1. Department of Cell Genetics, Sasaki Institute, 2-2, Kanda-Surugadai, Chiyoda-ku, 101-0062, Tokyo, Japan

    Fumiko Kihara-Negishi, Hitomi Yamamoto, Mitsuhiro Suzuki, Toshiyuki Yamada, Takuya Sakurai & Tsuneyuki Oikawa

  2. Department of Biology, Faculty of Science, Chiba University, 1-33, Yayoi-chyo, Chiba, 263-8522, Inage-ku, Japan

    Takaaki Tamura

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  1. Fumiko Kihara-Negishi
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Correspondence to Tsuneyuki Oikawa.

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Kihara-Negishi, F., Yamamoto, H., Suzuki, M. et al. In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated transcriptional repression. Oncogene 20, 6039–6047 (2001). https://doi.org/10.1038/sj.onc.1204756

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