A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory.
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-CD3repsilon/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 When the stimulatory signal is withdrawn, Oct-1 remains on the enhancer region as a stable marker of the stimulation, causing the second induction to be faster and stronger.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.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan.
Akiko
A
Murayama
Kazuhisa
K
Sakura
Mina
M
Nakama
Kayoko
K
Yasuzawa-Tanaka
Etsuko
E
Fujita
Yukiyo
Y
Tateishi
Yinan
Y
Wang
Toshikazu
T
Ushijima
Tadashi
T
Baba
Kazuko
K
Shibuya
Akira
A
Shibuya
Yoh-ichi
Y
Kawabe
Junn
J
Yanagisawa
D001943:Breast Neoplasms / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D019169:Jurkat Cells / Q000378:metabolism; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
D018106:CD28 Antigens; D006657:Histones; D007376:Interleukin-2; D050811:Octamer Transcription Factor-1