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A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory
Author(s) -
Murayama Akiko,
Sakura Kazuhisa,
Nakama Mina,
YasuzawaTanaka Kayoko,
Fujita Etsuko,
Tateishi Yukiyo,
Wang Yinan,
Ushijima Toshikazu,
Baba Tadashi,
Shibuya Kazuko,
Shibuya Akira,
Kawabe Yohichi,
Yanagisawa Junn
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601012
Subject(s) - biology , epigenetics , dna methylation , epigenetics of physical exercise , cpg site , dna demethylation , enhancer , demethylation , regulation of gene expression , methylation , gene expression , histone , microbiology and biotechnology , genetics , gene
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‐CD3ε/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 When the stimulatory signal is withdrawn, Oct‐1 remains on the enhancer region as a stable marker of the stimulation, causing the second induction to be faster and stronger.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.