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‐CD3e/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 When the stimulatory signal is withdrawn, Oct‐1 remains on the enhancer region as a stable marker of the stimulation, causing the second induction to be faster and stronger.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.