Journal
EMBO JOURNAL
Volume 25, Issue 5, Pages 1081-1092Publisher
WILEY
DOI: 10.1038/sj.emboj.7601012
Keywords
DNA demethylation; epigenetic memory; interleukin2; Oct-1; transcription
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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-CD3 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 When the stimulatory signal is withdrawn, Oct-1 remains on the enhancer region as a stable marker of the stimulation, causing the second induction to be faster and stronger.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.
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