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Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR

Oncogene volume 24, pages 1914–1923 (2005)Cite this article

Abstract

Epigenetic regulation of gene expression is critical in the maintenance of cellular homeostasis. Dysregulation of normal epigenetic transcription occurs in abnormal physiological conditions, such as those seen in cancer cells and cells infected with parasites, making the mechanism underlying abnormal epigenetic transcription of great interest. Gene expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by a viral transcriptional stimulator, Tax. We herein report a novel mechanism of transcription from the HTLV-1 long terminal repeat (LTR) that is regulated by Tax. In this study, we determined that Tax is able to activate transcription from the LTR, even when it was heavily methylated. In addition, the methyl-CpG-binding domain 2 (MBD2) protein played an important role in Tax-mediated transcriptional activation. We demonstrated the importance of a physical interaction between Tax and MBD2 in enhancing the transcriptional activity of Tax against the methylated LTR. Furthermore, we identified the formation of a protein complex composed of MBD2 and Tax bound to the methylated LTR. We propose a new model of epigenetic regulation by MBD2 acting in concert with a virally encoded transactivator, Tax. Our observation provides insight into the epigenetic regulation of gene expression and the diverse mechanisms of transcriptional regulation using methylated promoters.

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Acknowledgements

We thank Dr H Miyoshi for kindly providing the lentivirus-based gene expression system, Dr M Hatanaka for the pH2R-Tax expression plasmid, Dr M Maeda for ATL43Tb(−) cells, and Dr T Watanabe for MT-1 and TL-Om1 cells. We also thank Drs M Hijikata, K Watashi, and T Ohshima for their helpful discussion, and Ms N Umehara for supporting our work. This work was supported by grants-in-aid for research for the future from the Japan Society for the Promotion of Science and for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Takeshi Ego & Kunitada Shimotohno

  2. Immunology, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, 903-0215, Japan

    Yuetsu Tanaka

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  1. Takeshi Ego
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Correspondence to Kunitada Shimotohno.

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Ego, T., Tanaka, Y. & Shimotohno, K. Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR. Oncogene 24, 1914–1923 (2005). https://doi.org/10.1038/sj.onc.1208394

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