Surprisingly, we observed that an epigenetic modification e.g. histone modification regulates another epigenetic modification, a DNA methylation, indirectly via modulating a metabolic and tumor suppressor gene, IDH2. These results suggested that the cancer cells could benefit enormously if they were to hijack the WEE1/pY37-H2B epigenetic signaling to regulate DNA methylation in cells. This evidence concerns the gene H2BC21 and cancer.