In summary, our results indicate that green tea polyphenol EGCG and broccoli SFN can regulate both genetic and epigenetic mechanisms via, at least in part, directly inhibiting gene expression of two important epigenetic modulators, DNMT1 and HDAC1, leading to an opened chromatin structure and altered transcriptional factor binding status in the ERα promoter that may contribute to ERα transcriptional activation in ERα(−) breast cancer cells. The gene discussed is ESR1; the disease is breast cancer.