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  • The EMBO Journal (2006) 25, 1081 - 1092
  • doi:10.1038/sj.emboj.7601012

Published online: 23 February 2006

A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory

Akiko Murayama1, Kazuhisa Sakura1, Mina Nakama1, Kayoko Yasuzawa-Tanaka1, Etsuko Fujita1, Yukiyo Tateishi1, Yinan Wang2, Toshikazu Ushijima3, Tadashi Baba1, Kazuko Shibuya2, Akira Shibuya2, Yoh-ichi Kawabe1 and Junn Yanagisawa1

  1. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan
  2. Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, Center for TARA, University of Tsukuba, Ibaraki, Japan
  3. Carcinogenesis Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan

Correspondence to:

Junn Yanagisawa, Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tenno-dai, Tsukuba Science City, Ibaraki 305-8572, Japan. Tel.: +81 29 853 6632; Fax: 81 29 853 4605; E-mail: junny@agbi.tsukuba.ac.jp

Received 27 September 2005; Accepted 27 January 2006

DNA demethylation plays a critical role in transcriptional regulation in differentiated somatic cells. However, there is no experimental evidence that CpG methylation in a small region of a genome restricts gene expression. Here, we show that the anti-CD3alt epsilon/CD28 antibody stimulation of human CD4+ T cells induces IL2 expression following epigenetic changes, including active demethylation of a specific CpG site, recruitment of Oct-1, and changes in histone modifications. When the stimulatory signal is withdrawn, Oct-1 remains on the enhancer region as a stable marker of the stimulation, causing the second induction to be faster and stronger. Our observations indicate that Oct-1-binding followed by CpG demethylation are key events in the epigenetic regulation of IL2 expression and may act as a memory of the regulatory event.

  • Keywords:

    • DNA demethylation,
    • epigenetic memory,
    • interleukin-2,
    • Oct-1,
    • transcription